tag:theconversation.com,2011:/global/topics/nanomedicine-12397/articlesNanomedicine – The Conversation2023-09-06T12:26:19Ztag:theconversation.com,2011:article/2054612023-09-06T12:26:19Z2023-09-06T12:26:19ZCould a single drug treat the two leading causes of death in the US: cancer and cardiovascular disease?<figure><img src="https://images.theconversation.com/files/545343/original/file-20230829-19-am4x6.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2158%2C1387&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Identifying the commonalities between cardiovascular disease and cancer could lead to improved treatments for both.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/heart-treatment-concept-royalty-free-image/1291438248">Sveta Zi/iStock via Getty Images Plus</a></span></figcaption></figure><p>What would you guess are the two biggest killers in the world? Based on media coverage, maybe you guessed gun violence, accidents or COVID-19. But the top two killers are actually cardiovascular disease and cancer. These two diseases combined account for <a href="https://doi.org/10.1161/CIRCULATIONAHA.120.051451">nearly 50% of deaths in the U.S</a>. </p>
<p>Cardiovascular disease and cancer seem to be quite different on the surface. But <a href="https://doi.org/10.1021/acsnano.0c00245">newly discovered parallels</a> between the origins and development of these two diseases mean that some treatments may be effective against both. </p>
<p>I am a <a href="https://scholar.google.com/citations?user=wD6KbXkAAAAJ&hl=en">biomedical engineer</a> who has spent two decades studying and developing ways to improve how drugs travel through the body. It turns out that tiny, engineered nanoparticles that can target specific immune cells may be a way to treat both cancer and cardiovascular disease.</p>
<h2>Cardiovascular disease and cancer</h2>
<p><a href="https://www.nhlbi.nih.gov/health/atherosclerosis">Atherosclerosis</a> is the most deadly form of cardiovascular disease. It <a href="https://doi.org/10.1161/hc0902.104353">results from</a> inflammation and the buildup of fat, cholesterol and <a href="https://www.khanacademy.org/science/biology/macromolecules/lipids/a/lipids">other lipids</a> in the blood vessel wall, forming a plaque. Most heart attacks are caused by <a href="https://doi.org/10.1161/CIRCRESAHA.114.302721">plaque rupture</a>. The body’s attempt to heal the wound can form a blood clot that blocks blood vessels and result in a heart attack.</p>
<p>On the other hand, cancer usually arises from genetic mutations that make cells divide uncontrollably. Unrestrainable, rapid cell growth that is untreated can be destructive because it is difficult to stop without harming healthy organs. Cancer can start from and occur in <a href="https://theconversation.com/every-cancer-is-unique-why-different-cancers-require-different-treatments-and-how-evolution-drives-drug-resistance-199249">any organ of the body</a>. </p>
<p>Although cardiovascular disease and cancer appear to have different origins and causes, they <a href="https://doi.org/10.1161/CIRCULATIONAHA.115.020406">share many risk factors</a>. For example, obesity, smoking, chronic stress and certain lifestyle choices like poor diet are linked to both diseases. Why might these two diseases share similar risk factors? </p>
<p>Many of the similarities between cardiovascular disease and cancer can be traced to inflammation. Chronic inflammation is a <a href="https://doi.org/10.1161/hc0902.104353">primary cause of atherosclerosis</a> by damaging the cells lining the blood vessels and progressively worsening plaques. Likewise, chronic inflammation can <a href="https://doi.org/10.1016/j.immuni.2019.06.025">initiate cancer</a> by increasing mutations and <a href="https://doi.org/10.1038/nature01322">support cancer cell survival and spread</a> by increasing the growth of the blood vessels that feed them nutrients and suppressing the body’s immune response.</p>
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<figcaption><span class="caption">Cardiovascular disease and cancer share many risk factors.</span></figcaption>
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<h2>Treating two conditions at once</h2>
<p>Research hints that therapies designed for cancer can also help treat atherosclerosis. </p>
<p>One example is drugs that target immune cells called macrophages in tumors and <a href="https://doi.org/10.1016/j.cell.2009.05.045">cause them to eat</a> <a href="https://doi.org/10.1172/jci81603">cancer cells</a>. It turns out a similar drug can cause macrophages to <a href="https://doi.org/10.1038/nature18935">clear dead and dying cells</a> in atherosclerosis, which shrinks plaques. </p>
<p>Another example are antiglycolytic therapies that prevent the breakdown of glucose. <a href="https://www.khanacademy.org/science/ap-biology/chemistry-of-life/properties-structure-and-function-of-biological-macromolecules/a/carbohydrates">Glucose, or sugar</a>, is the body’s main source of energy. These drugs can make diseased <a href="https://doi.org/10.1016/j.ccell.2016.10.006">tumor blood vessels</a> and <a href="https://doi.org/10.1021/acsnano.8b08875">atherosclerotic blood vessels</a> look more “normal,” essentially reversing the disease process in those vessels. They can also reduce inflammation in atherosclerosis.</p>
<p>Although <a href="https://doi.org/10.1161/CIR.0000000000000678">currently marketed treatments</a> like statins and fibrates can lower lipid levels and blood clotting in atherosclerosis, these drugs have not sufficiently addressed the risk of death from cardiovascular disease. To improve outcomes, clinicians are increasingly using multiple drugs directed against different targets. One intriguing class of treatments is sodium glucose cotransporter-2 inhibitors, which are traditionally used to treat diabetes. Researchers have shown that these drugs both provide significant protection from <a href="https://doi.org/10.1161/CIR.0000000000000678">cardiovascular disease</a> and <a href="https://doi.org/10.1073/pnas.1511698112">treat cancer</a>. </p>
<p>Clinical trials on statins and sodium glucose cotransporter-2 inhibitors indicate a close overlap between inflammation, metabolism and cardiovascular disease that suggests new treatment opportunities. One example is immunotherapies that “inhibit the inhibition” of immunity – that is, they take off the brakes that tumors place on the immune system. This approach to <a href="https://doi.org/10.3389/fphar.2021.731798">treat cancer</a> also <a href="https://doi.org/10.1038/s44161-023-00232-y">reduced atherosclerotic</a> <a href="https://doi.org/10.1007/s12274-020-3111-3">plaques in</a> <a href="https://doi.org/10.1038/s41565-019-0619-3">animal studies</a> and <a href="https://doi.org/10.1056/NEJMc2029834">reduced vascular inflammation</a> in a small study in people. </p>
<h2>A nanomedical Trojan horse</h2>
<p>A recent discovery showed that nanotubes – a very small particle made of carbon that is over 10,000 times thinner than a human hair – can go into specific immune cells, travel through the bloodstream and enter tumors <a href="https://doi.org/10.1038%2Fnnano.2014.62">as a Trojan horse</a>. These nanotubes can carry anything that researchers put on them, including drugs and imaging contrast agents.</p>
<p>The immune cells carrying the nanotubes naturally <a href="https://doi.org/10.4049/jimmunol.0902583">home in on tumors</a> through the inflammatory response. Since cancer and atherosclerosis are both inflammatory diseases, my research team and I have been studying whether nanotube-loaded immune cells may also serve as delivery vehicles to plaques. </p>
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<figcaption><span class="caption">Nanoparticles can be used to “eat” the plaques that cause heart disease.</span></figcaption>
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<p>Nanotubes can be loaded with a therapy that stimulates immune cells to <a href="https://doi.org/10.1038/s41565-019-0619-3">“eat” plaque debris</a> and thus reduce plaque size. Moreover, restricting drug delivery specifically to those immune cells reduces the risk of off-target side effects. These nanotubes can also be used to improve <a href="https://doi.org/10.1002/adfm.202101005">diagnosis of cardiovascular disease</a> by highlighting plaques.</p>
<p>Another way nanoparticles can enter tumors is by squeezing through openings in new blood vessels grown in inflammatory conditions. This is known as the <a href="https://doi.org/10.1016/s0168-3659(99)00248-5">enhanced permeation and retention effect</a>, where larger molecules and nanoparticles accumulate in tissues with leaky blood vessels and remain there for some time because of their size. First <a href="https://doi.org/10.1016%2Fj.bpj.2018.07.038">discovered in cancer</a>, researchers are applying this effect to improve drug delivery for <a href="https://doi.org/10.1073/pnas.1322725111">cardiovascular disease</a>, which can also involve <a href="https://doi.org/10.1016/j.biomaterials.2016.05.018">leaky blood vessels</a>.</p>
<h2>Improving drug development</h2>
<p>The molecular pathways cancer and cardiovascular disease share have important regulatory implications. The <a href="https://theconversation.com/90-of-drugs-fail-clinical-trials-heres-one-way-researchers-can-select-better-drug-candidates-174152">costs involved</a> in getting drugs into the clinic are enormous. The possibility of <a href="https://theconversation.com/repurposing-generic-drugs-can-reduce-time-and-cost-to-develop-new-treatments-but-low-profitability-remains-a-barrier-174874">applying the same drug</a> to two different patient populations offers big financial and risk-reduction incentives. It also offers the potential for simultaneous treatment for patients with both diseases.</p>
<p><a href="https://theconversation.com/nanoparticles-are-the-future-of-medicine-researchers-are-experimenting-with-new-ways-to-design-tiny-particle-treatments-for-cancer-180009">Nanoparticle-based cancer drugs</a> first <a href="https://doi.org/10.1016/j.jconrel.2012.03.020">entered the clinic in 1995</a>, and researchers have developed many others since. But there is currently only <a href="https://doi.org/10.1592/phco.28.5.570">one cardiovascular nanodrug</a> approved by the Food and Drug Administration. This suggests opportunity for new <a href="https://doi.org/10.1038/s41569-021-00594-5">nanotherapy approaches</a> to <a href="https://doi.org/10.1038/s44161-023-00232-y">improve cardiovascular drug</a> efficacy and reduce side effects.</p>
<p>Because of the parallels between cancer and cardiovascular disease, cancer nanodrugs may be strong drug candidates to treat cardiovascular disease and vice versa. As basic science discovers other molecular parallels between these diseases, patients will be the beneficiaries of better therapies that can treat both.</p><img src="https://counter.theconversation.com/content/205461/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bryan Smith receives funding from the National Institutes of Health (the National Cancer Institute) and the Juvenile Diabetes Research Foundation. He has received funding from the American Heart Association, the American Association for Cancer Research, and the Ralph and Marian Falk Medical Research Trust. </span></em></p>Cardiovascular disease and cancer share many parallels in their origins and how they develop. Nanoparticles offer one potential way to effectively treat both with reduced side effects.Bryan Smith, Associate Professor of Biomedical Engineering, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1966522023-01-05T13:26:24Z2023-01-05T13:26:24ZNanomedicines for various diseases are in development – but research facilities produce vastly inconsistent results on how the body will react to them<figure><img src="https://images.theconversation.com/files/502207/original/file-20221220-6047-jjdm3d.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C1637&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanoparticles (white disks) can be used to deliver treatment to cells (blue).</span> <span class="attribution"><a class="source" href="https://flic.kr/p/KjvnhT">Brenda Melendez and Rita Serda/National Cancer Institute, National Institutes of Health</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p><a href="https://doi.org/10.3389/fchem.2018.00360">Nanomedicines</a> took the spotlight during the COVID-19 pandemic. Researchers are using these very small and intricate materials to develop diagnostic tests and treatments. Nanomedicine is already used for various diseases, such as the <a href="https://doi.org/10.1038/s41565-020-0757-7">COVID-19 vaccines</a> and therapies for <a href="https://doi.org/10.1038/nnano.2017.167">cardiovascular disease</a>. The “nano” refers to the use of particles that are only a few hundred nanometers in size, which is <a href="https://www.nano.gov/nanotech-101/what/nano-size">significantly smaller than</a> the width of a human hair.</p>
<p>Although researchers have developed <a href="https://doi.org/10.1007/s40820-022-00922-5">several methods</a> to improve the reliability of nanotechnologies, the field still faces one major roadblock: a lack of a standardized way to analyze <a href="https://doi.org/10.1016/j.tibtech.2016.08.011">biological identity</a>, or how the body will react to nanomedicines. This is essential information in evaluating how effective and safe new treatments are. </p>
<p>I’m a researcher studying <a href="https://scholar.google.com/citations?user=D-qg1JwAAAAJ&hl=en">overlooked factors in nanomedicine development</a>. In our <a href="https://doi.org/10.1038/s41467-022-34438-8">recently published research</a>, my colleagues and I found that analyses of biological identity are highly inconsistent across proteomics facilities that specialize in studying proteins.</p>
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<figcaption><span class="caption">Gold is one of the materials used in nanotechnologies.</span></figcaption>
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<h2>Inconsistent results</h2>
<p>Nanomedicines, just like with all medications, are surrounded by proteins from the body once they come into contact with the bloodstream. This protein coating, known as a <a href="https://doi.org/10.1016/j.ijbiomac.2020.12.108">protein corona</a>, gives nanoparticles a biological identity that determines how the body will recognize and interact with it, like how the immune system has specific reactions against certain pathogens and allergens.</p>
<p>Knowing the precise type, amount and configuration of the proteins and other biomolecules attached to the surface of nanomedicines is critical to determine safe and effective dosages for treatments. However, one of the <a href="https://doi.org/10.1038/s41467-021-27643-4">few available approaches</a> to analyze the composition of protein coronas requires instruments that many nanomedicine laboratories lack. So these labs typically send their samples to separate proteomics facilities to do the analysis for them. Unfortunately, many facilities use <a href="https://doi.org/10.1038/s41587-019-0037-y">different sample preparation methods and instruments</a>, which can lead to differences in results.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Cryo-electron microscopy images of protein coronas on nanoparticles" src="https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/502192/original/file-20221220-20-iflyr8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Protein coronas give nanoparticles their biological identities. Images A to C show nanoparticles without protein coronas, while images D to F show proteins (black dots) coating the surface of the particles.</span>
<span class="attribution"><a class="source" href="https://doi.org/10.1038/s41467-022-34438-8">Ashkarran et al. (2022)/Nature Communications</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>We wanted to test how consistently these proteomics facilities analyzed protein corona samples. To do this, my colleagues and I sent biologically identical protein coronas to 17 different labs in the U.S. for analysis. </p>
<p>We had striking results: <a href="https://doi.org/10.1038/s41467-022-34438-8">Less than 2%</a> of the proteins the labs identified were the same. </p>
<p>Our results reveal an extreme lack of consistency in the analyses researchers use to understand how nanomedicines work in the body. This may pose a significant challenge not only to ensuring the accuracy of diagnostics, but also the effectiveness and safety of treatments based on nanomedicines.</p>
<h2>Why standardize nanomedicine?</h2>
<p>Researchers have been working to improve the safety and efficacy of nanomedicine through various approaches. These include modifying study protocols, methodologies and analytical techniques to <a href="https://doi.org/10.1038/s41565-018-0246-4">standardize the field</a> and improve the reliability of nanomedicine data.</p>
<p>Aligned with these efforts, my team and I have identified several critical but often overlooked factors that can influence the performance of a nanomedicine, such as a <a href="https://doi.org/10.1038/s41467-021-23230-9">person’s sex</a>, <a href="https://doi.org/10.1039/C4BM00131A">prior medical conditions</a> and <a href="https://doi.org/10.1039/C9NH00097F">disease type</a>. Taking these factors into account when designing studies and interpreting results could enable researchers to produce more reliable and accurate data and lead to better nanomedicine treatments.</p><img src="https://counter.theconversation.com/content/196652/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Morteza Mahmoudi receives funding from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (grant DK131417). He is affiliated with PGWC, NanoServ, and Target's Tip. He is a co-founder and director of the Academic Parity Movement (<a href="http://www.paritymovement.org">www.paritymovement.org</a>), a non-profit organization dedicated to addressing academic discrimination, violence and incivility. He receives royalties/honoraria for his published books, plenary lectures, and licensed patents. </span></em></p>The proteins that cover nanoparticles are essential to understanding how they work in the body. Across 17 proteomics facilities in the US, less than 2% of the identified proteins were identical.Morteza Mahmoudi, Assistant Professor of Radiology, Michigan State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1800092022-05-04T18:02:21Z2022-05-04T18:02:21ZNanoparticles are the future of medicine – researchers are experimenting with new ways to design tiny particle treatments for cancer<figure><img src="https://images.theconversation.com/files/461078/original/file-20220503-38813-i2h2zm.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanoparticles can help cancer drugs home in on tumors and avoid damaging healthy cells.
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/destruction-of-a-cancer-cell-illustration-royalty-free-illustration/713780459">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>When you hear the word “nanomedicine,” it might call to mind scenarios like those in the 1966 movie “<a href="https://www.youtube.com/watch?v=dO5E4wkg0hA">Fantastic Voyage</a>.” The film portrays a medical team shrunken down to ride a microscopic robotic ship through a man’s body to clear a blood clot in his brain. </p>
<p>Nanomedicine has not reached that level of sophistication yet. Although scientists can generate nanomaterials smaller then several nanometers – the “nano” indicating one-billionth of a meter – today’s nanotechnology has not been able to generate functional electronic robotics tiny enough to inject safely into the bloodstream. But since the <a href="https://doi.org/10.1038/nnano.2006.115">concept of nanotechnology</a> was first introduced in the 1970s, it has made its mark in many everyday products, including electronics, fabrics, food, water and air treatment processes, cosmetics and drugs. Given these successes across different fields, many medical researchers were eager to use nanotechnology to diagnose and treat disease.</p>
<p>I am a <a href="https://scholar.google.com/citations?user=Ufab1aYAAAAJ&hl=en">pharmaceutical scientist</a> who was inspired by the promise of nanomedicine. <a href="https://pharmacy.umich.edu/sun-lab">My lab</a> has worked on developing cancer treatments using nanomaterials over the past 20 years. While nanomedicine has seen many successes, some researchers like me have been disappointed by its <a href="https://doi.org/10.1016/j.jconrel.2019.05.044">underwhelming overall performance</a> in cancer. To better translate success in the lab to treatments in the clinic, we proposed a <a href="https://doi.org/10.1021/acsnano.9b09713">new way to design</a> cancer drugs using nanomaterials. Using this strategy, we <a href="https://www.science.org/doi/10.1126/scitranslmed.abl3649">developed a treatment</a> that was able to achieve full remission in mice with metastatic breast cancer. </p>
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<figcaption><span class="caption">While nanomedicine isn’t “Fantastic Voyage,” it shares the film’s treatment goal of delivering a drug exactly where it needs to go.</span></figcaption>
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<h2>What is nanomedicine?</h2>
<p><a href="https://doi.org/10.1021/acsnano.9b09713">Nanomedicine</a> refers to the use of materials at the nanoscale to diagnose and treat disease. Some researchers define nanomedicine as encompassing any medical products using nanomaterials smaller than 1,000 nanometers. Others more narrowly use the term to refer to injectable drugs using nanoparticles smaller than 200 nanometers. Anything larger may not be safe to inject into the bloodstream.</p>
<p>Several nanomaterials have been successfully used in vaccines. The most well-known examples today are the <a href="https://doi.org/10.1016/j.ijpharm.2021.120586">Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines</a>. These vaccines used a nanoparticle made of of lipids, or fatty acids, that helps carry the mRNA to where it needs to go in the body to trigger an immune response.</p>
<p>Researchers have also successfully used nanomaterials in diagnostics and medical imaging. <a href="https://www.fda.gov/media/145080/download">Rapid COVID-19 tests</a> and <a href="https://doi.org/10.1016/s1028-4559(08)60127-8">pregnancy tests</a> use gold nanoparticles to form the colored band that designates a positive result. <a href="https://doi.org/10.1186/s13244-019-0771-1">Magnetic resonance imaging, or MRI</a>, often uses nanoparticles as contrast agents that help make an image more visible.</p>
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<figcaption><span class="caption">Gold is one type of nanoparticle whose uses researchers are testing in a range of contexts.</span></figcaption>
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<p>Several nanoparticle-based drugs have been approved for cancer treatment. <a href="https://doi.org/10.1016/j.jconrel.2012.03.020">Doxil (doxorubicin)</a> and <a href="https://dx.doi.org/10.4172%2F2157-7439.1000164">Abraxane (paclitaxel)</a> are chemotherapy drugs that use nanomaterials as a delivery mechanism to improve treatment efficacy and reduce side effects.</p>
<h2>Cancer and nanomedicine</h2>
<p>The potential of nanomedicine to improve a drug’s effectiveness and reduce its toxicity is attractive for cancer researchers working with anti-cancer drugs that often have strong side effects. Indeed, <a href="https://doi.org/10.1016/j.jconrel.2020.07.007">65% of clinical trials using nanoparticles</a> are focused on cancer.</p>
<p>The idea is that nanoparticle cancer drugs could <a href="https://doi.org/10.1021/acsnano.9b09713">act like biological missiles</a> that destroy tumors while minimizing damage to healthy organs. Because tumors have leaky blood vessels, researchers believe this would allow nanoparticles to <a href="https://dx.doi.org/10.1021%2Facs.bioconjchem.6b00437">accumulate in tumors</a>. Conversely, because nanoparticles can circulate in the bloodstream longer than traditional cancer treatments, they could accumulate less in healthy organs and reduce toxicity. </p>
<p>Although these design strategies have been successful in mouse models, most nanoparticle cancer drugs have <a href="https://doi.org/10.1021/acsnano.9b09713">not been shown</a> to be more effective than other cancer drugs. Furthermore, while some nanoparticle-based drugs can reduce toxicity to certain organs, they may increase toxicity in others. For example, while the nanoparticle-based <a href="https://doi.org/10.1007/s13577-012-0057-0">Doxil</a> decreases damage to the heart compared with other chemotherapy options, it can increase the risk of developing <a href="https://www.cancer.net/coping-with-cancer/physical-emotional-and-social-effects-cancer/managing-physical-side-effects/hand-foot-syndrome-or-palmar-plantar-erythrodysesthesia">hand-foot syndrome</a>.</p>
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<figcaption><span class="caption">The COVID-19 mRNA vaccines spurred excitement about nanoedicine’s potential applications to other diseases.</span></figcaption>
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<h2>Improving nanoparticle-based cancer drugs</h2>
<p>To investigate ways to improve how nanoparticle-based cancer drugs are designed, my research team and I <a href="https://doi.org/10.1016/j.biomaterials.2021.120910">examined how well</a> five approved nanoparticle-based cancer drugs accumulate in tumors and avoid healthy cells compared with the same cancer drugs without nanoparticles. Based on the findings of our lab study, we proposed that designing nanoparticles to be <a href="https://doi.org/10.1021/acsnano.9b09713">more specific</a> to their intended target could improve their translation from animal models to people. This includes creating nanoparticles that address the shortcomings of a particular drug – such as common side effects – and home in on the types of cells they should be targeting in each particular cancer type.</p>
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<p>Using these criteria, we designed a <a href="https://www.science.org/doi/10.1126/scitranslmed.abl3649">nanoparticle-based immunotherapy</a> for metastatic breast cancer. We first identified that breast cancer has a type of immune cell that suppresses immune response, helping the cancer become resistant to treatments that stimulate the immune system to attack tumors. We hypothesized that while drugs could overcome this resistance, they are unable to sufficiently accumulate in these cells to succeed. So we designed nanoparticles made of a common protein called albumin that could deliver cancer drugs directly to where these immune-suppressing cells are located.</p>
<p>When we tested our nanoparticle-based treatment on mice genetically modified to have breast cancer, we were able to eliminate the tumor and achieve complete remission. All of the mice were still alive 200 days after birth. We’re hopeful it will eventually translate from animal models to cancer patients.</p>
<h2>Nanomedicine’s bright but realistic future</h2>
<p>The success of some drugs that use nanoparticles, such as the <a href="https://doi.org/10.1038/d41586-021-02483-w">COVID-19 mRNA vaccines</a>, has prompted excitement among researchers and the public about their potential use in treating various other diseases, including talks about a future <a href="https://doi.org/10.1038/d41573-021-00110-x">cancer vaccine</a>. However, a vaccine for an infectious disease is <a href="https://doi.org/10.1186/s12943-021-01335-5">not the same</a> as a vaccine for cancer. Cancer vaccines may require different strategies to overcome treatment resistance. Injecting a nanoparticle-based vaccine into the bloodstream also has different design challenges than injecting into muscle.</p>
<p>While the field of nanomedicine has made good progress in getting drugs or diagnostics out of the lab and into the clinic, it still has a long road ahead. Learning from past successes and failures can help researchers develop breakthroughs that allow nanomedicine to live up to its promise.</p><img src="https://counter.theconversation.com/content/180009/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Duxin Sun receives funding from NIH, FDA and Pharmaceutical Industries for his lab research at The University of Michigan. </span></em></p>The COVID-19 mRNA vaccines put nanomedicine in the spotlight as a potential way to treat diseases like cancer and HIV. While the field isn’t there yet, better design could help fulfill its promise.Duxin Sun, Professor of Pharmaceutical Sciences, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1692622021-10-06T19:01:35Z2021-10-06T19:01:35ZWe created a microscope slide that could improve cancer diagnosis, by revealing the ‘colour’ of cancer cells<figure><img src="https://images.theconversation.com/files/424927/original/file-20211006-27-1r03a5g.jpeg?ixlib=rb-1.1.0&rect=31%2C18%2C1478%2C1113&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption"></span> <span class="attribution"><span class="license">Author provided</span></span></figcaption></figure><p>When we look at biological cells under a microscope, they’re usually not very colourful. Normally, to visualise them we have to artificially add colour — typically by staining. By doing so, we can see their shape and arrangement in a tissue and determine whether they’re healthy or not. </p>
<p>Sometimes, though, cell structure alone isn’t enough to accurately identify disease — which can lead to misdiagnosis and potentially fatal consequences for a patient. But what if there was a way to not only see the structure of cells, but also determine whether they are abnormal, simply by looking at their intrinsic colour under a microscope? </p>
<p>This was our team’s goal as we developed a new medical diagnostic tool called the NanoMslide. We modified a standard microscope slide to turn it into a powerful tool for breast cancer detection. Our <a href="https://www.nature.com/articles/s41586-021-03835-2">research</a> is published today in Nature.</p>
<h2>Early detection is key</h2>
<p>It’s <a href="https://www.canceraustralia.gov.au/cancer-types/breast-cancer/statistics">estimated</a> one in eight Australian women will be diagnosed with breast cancer by age 85. As with most cancers, catching the disease early is critical. However, an accurate diagnosis of the earliest stages of breast cancer requires identifying small numbers of diseased cells throughout a tissue, which can be incredibly challenging. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Human cancerous tissue viewed under miscroscope" src="https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424928/original/file-20211006-13-z19h5s.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Human cancerous tissue, viewed through a microscope with the NanoMslide applied.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424930/original/file-20211006-27-7p7upy.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Normal (non-cancerous) human tissue, viewed through a microscope with the NanoMslide applied.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The NanoMslide can manipulate light at the nanoscale, causing cells to “light up” with vivid colour contrast. This makes it easier to recognise potentially cancerous cells (or benign abnormalities) within the tissue. </p>
<p>By providing a way to instantly distinguish which cells could be cancerous, the tool may help to reduce current uncertainty around very early-stage breast cancer detection. With mammogram screening, distinguishing breast abnormalities from early breast cancers upon biopsy is very important, particularly as misdiagnosis rates can be as high as 15%.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/devastated-and-sad-after-36-years-of-research-early-detection-of-ovarian-cancer-doesnt-save-lives-160999">'Devastated and sad' after 36 years of research — early detection of ovarian cancer doesn't save lives</a>
</strong>
</em>
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<h2>Major barriers in development</h2>
<p>Incorporating nanotechnology into medical diagnostics presents a number of challenges. It took us six years of development to ensure NanoMslide would work effectively. In the end it was a combination of cutting-edge nanofabrication, a significant amount of trial-and-error and a bit of good fortune that led to our breakthrough.</p>
<p>For decades, researchers have known cancer cells tend to interact with light in a way that’s different to healthy cells. This is due to a variety of factors, such as the distribution of protein inside the cell and differences in its overall shape. </p>
<p>The main challenge is these differences can be extremely subtle and can present in a variety of ways. Previous approaches to differentiating cancer cells (without using stains or labels) have tended to use specialised microscopy equipment, or complex techniques. </p>
<p>But these approaches are difficult to incorporate into existing pathology workflows and can require specialist training and knowledge. So we took a radically different approach. </p>
<h2>Success with human tissue</h2>
<p>Rather than focusing on developing a better microscope, we focused on improving the microscope slide instead. </p>
<p>By developing a special nanofabricated coating, we modified the surface of an ordinary microscope slide and transformed it into one huge sensor. What’s truly remarkable is the structures of the sensor are just a few hundred nanometres across, yet are repeated with amazing precision across an area of tens of centimetres, or more. </p>
<p>Maintaining this level of precision, which is necessary for reliable fabrication at this scale, has taken advances in nanofabrication techniques that have only become commercially available in the past six years.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=292&fit=crop&dpr=1 600w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=292&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=292&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=367&fit=crop&dpr=1 754w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=367&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/424931/original/file-20211006-28-g3l0li.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=367&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The NanoMslide is a large sensor fitted with cutting-edge nanotechnology capabilities.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>The sensor is activated by visible light. And when an object such as a tissue or single cell comes into contact with the sensor’s surface, colours are produced. It is this feature which we’ve been able to optimise to allow pathologists to detect cells that are likely cancerous, just by looking at them.</p>
<p>The dyes which are currently used to stain tissues (to visualise cell shape and architecture) normally present as one or two colours. The NanoMslide renders tissues in beautiful full-colour contrast, making it easier to differentiate multiple types of cell on a single slide. </p>
<p>For our study, we tested the slides with expert breast-cancer pathologists, using both a mouse model and patient tissue. By starting with a well-characterised small-animal model, our team of physicists, cancer researchers and breast pathologists was able to develop the technology further. </p>
<p>We eventually reached the point where we could be confident some of the specific colours visible were indicative of cancerous cells. This led to further pathology assessments with patient tissue, where there is more complexity to contend with in terms of diagnosis. </p>
<p>Yet, even in this more challenging setting, the NanoMslide performed strongly. It also outperformed some commercial biomarkers, which are used as an aid for borderline diagnoses (where cancer is difficult to tell apart from benign abnormalities).</p>
<h2>Like going from black and white to colour television</h2>
<p>Because the technology doesn’t rely on any special function, or specific molecular interactions, it could potentially be applied to other types of cancer — even other types of disease. Another application now being worked on is to examine the results of liquid biopsies, such as cheek swabs, for immediate point-of-care analysis.</p>
<p>In April, we were fortunate to benefit from the opening of a new instrument at the Australian National Fabrication Facility to enable the scaling-up of production. This means NanoMslide can be moved from small-scale to medium-scale manufacture, allowing us to explore a number of different applications, and produce the numbers of slides required for further clinical validation. </p>
<p>The technology could also be hugely beneficial to the growing digital-pathology space, where the vivid colours generated by NanoMslide could help develop next-generation artificial intelligence algorithms to identify signs of disease. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/curious-kids-why-do-people-get-cancer-106069">Curious Kids: Why do people get cancer?</a>
</strong>
</em>
</p>
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<img src="https://counter.theconversation.com/content/169262/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Brian Abbey receives funding from the Australian Research Council (ARC).</span></em></p><p class="fine-print"><em><span>Belinda Parker receives funding from the DHHS, National Breast Cancer Foundation, Prostate Cancer Foundation Australia, Movember, and the Peter MacCallum Cancer Foundation. </span></em></p>The NanoMslide causes potentially cancerous cells to ‘light up’ with vivid colour contrast. It has already been successful in finding early-stage breast cancer cells in human tissue.Brian Abbey, Professor of Physics, La Trobe UniversityBelinda Parker, Senior Faculty/Laboratory Head, Peter MacCallum Cancer CentreLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1451402020-09-07T13:13:34Z2020-09-07T13:13:34ZCoronavirus nanoscience: the tiny technologies tackling a global pandemic<figure><img src="https://images.theconversation.com/files/356743/original/file-20200907-16-7xd8as.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/antibodies-attacking-sarscov2-virus-conceptual-3d-1700617951">Kateryna Kon/Shutterstock</a></span></figcaption></figure><p>The world-altering coronavirus behind the COVID-19 pandemic is thought to be just <a href="https://www.sciencedirect.com/science/article/pii/S2090123220300540">60 nanometres to 120 nanometres</a> in size. This is so mind bogglingly small that you could fit more than 400 of these virus particles into the width of a single hair on your head. In fact, coronaviruses are so small that <a href="https://theconversation.com/five-techniques-were-using-to-uncover-the-secrets-of-viruses-144363">we can’t see them</a> with normal microscopes and require much fancier electron microscopes to study them. How can we battle a foe so minuscule that we cannot see it?</p>
<p>One solution is to fight tiny with tiny. <a href="https://www.nano.gov/nanotech-101/what/definition">Nanotechnology</a> relates to any technology that is or contains components that are between 1nm and 100nm in size. Nanomedicine that takes advantage of such tiny technology is used in everything from plasters that contain anti-bacterial nanoparticles of silver to <a href="https://www.eurekaselect.com/132451/article">complex diagnostic machines</a>. </p>
<p>Nanotechnology also has an impressive record against viruses and has been used since the <a href="https://www.longdom.org/open-access/history-and-possible-uses-of-nanomedicine-based-on-nanoparticles-and-nanotechnological-progress-2157-7439-1000336.pdf">late 1880s</a> to separate and identify them. More recently, nanomedicine has been used to develop treatments for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507392/">flu, Zika and HIV</a>. And now it’s joining the fight against the COVID-19 virus, SARS-CoV-2.</p>
<h2>Diagnosis</h2>
<p>If you’re suspected of having COVID, swabs from your throat or nose will be taken and tested by reverse transcription polymerase chain reaction (<a href="https://www.iaea.org/newscenter/news/how-is-the-covid-19-virus-detected-using-real-time-rt-pcr">RT-PCR</a>). This method checks if genetic material from the coronavirus is present in the sample. </p>
<p>Despite being highly accurate, the test can take <a href="https://www.nhs.uk/conditions/coronavirus-covid-19/testing-and-tracing/what-your-test-result-means/">up to three days</a> to produce results, requires high-tech equipment only <a href="https://www.tandfonline.com/doi/full/10.1080/14787210.2020.1776115">accessible in a lab</a>, and can only tell if you have an active infection when the test is taken. But antibody tests, which check for the presence of <a href="https://www.ouh.nhs.uk/patient-guide/leaflets/files/66122Pantibody.pd">coronavirus antibodies</a> in your blood, can produce results immediately, wherever you’re tested. </p>
<p><a href="https://www.livescience.com/antibodies.html">Antibodies</a> are formed when your body fights back against a virus. They are tiny proteins that search for and destroy invaders by hunting for the chemical markers of germs, called antigens. This means antibody tests can not only tell if you have coronavirus but if you have previously had it. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241732/">Antibody tests use</a> nanoparticles of materials such as gold to capture any antibodies from a blood sample. These then slowly travel along a small piece of paper and stick to an antigen test line that only the coronavirus antibody will bond to. This makes the line visible and indicates that antibodies are present in the sample. These tests are more than <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295501/">95% accurate</a> and can give results <a href="https://www.briancolemd.com/wp-content/themes/ypo-theme/pdf/fast-portable-tests-come-online-to-curb-coronavirus-pandemic.pdf">within 15 minutes</a>. </p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/YdvFhIF1QEw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
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<h2>Vaccines and treatment</h2>
<p>A major turning point in the battle against coronavirus will be the development of a <a href="https://www.bbc.co.uk/news/health-51665497">successful vaccine</a>. Vaccines often contain an inactive form of a virus that acts as an antigen to train your immune system and enable it develop antibodies. That way, when it meets the real virus, your immune system is ready and able to resist infection. </p>
<p>But there are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180194/">some limitations</a> in that typical vaccine material can prematurely break down in the bloodstream and does not always reach the target location, reducing the efficiency of a vaccine. One solution is to enclose the vaccine material inside a nanoshell by a process called <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464443/">encapsulation</a>. </p>
<p>These shells are made from fats called lipids and can be as thin as <a href="https://www.sciencedirect.com/science/article/pii/S154996341200754X?casa_token=MLdBN28OW80AAAAA:pUBR_sctSnKf52ryvEY_gTDb22AdCHHzc71DVcpFADw7OYEogopmjVs5kx-sIoytavAitMWxAA">5nm in diameter</a>, which is 50,000 times thinner than an egg shell. The nanoshells protect the inner vaccine from breaking down and can also <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180194/">be decorated</a> with molecules that target specific cells to make them more effective at delivering their cargo. </p>
<p>This can improve the immune <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325519/#ref233">response of elderly people</a> to the vaccine. And critically, people typically need lower doses of these encapsulated vaccines to develop immunity, meaning you can more quickly produce enough to vaccinate an <a href="https://pubmed.ncbi.nlm.nih.gov/19059004/">entire population</a>. </p>
<p>Encapsulation can also improve viral treatments. A major contribution to the deaths of virus patients in intensive care is “acute respiratory distress syndrome”, which occurs when the immune system produces an <a href="https://pubs.acs.org/doi/10.1021/acsnano.0c03697">excessive response</a>. Encapsulated vaccines can target specific areas of the body to deliver immunosuppressive drugs directly to targeted organs and helping regulate our immune system response.</p>
<h2>Transmission reduction</h2>
<p>It’s hard to exaggerate the importance of wearing face masks and washing your hands to reducing the spread of COVID-19. But typical face coverings can have trouble stopping the most penetrating particles of respiratory droplets, and many can only be used once. </p>
<p>New fabrics made from nanofibres 100nm thick and coated in titanium oxide can catch droplets smaller than 1,000nm and so they can be destroyed by <a href="https://link.springer.com/article/10.1007/s11051-009-9820-x">ultraviolet (UV) radiation</a> from sunlight. <a href="https://news.kaist.ac.kr/newsen/html/news/?mode=V&mng_no=6530&skey=&sval=&list_s_date=&list_e_date=&GotoPage=1">Masks</a>, gloves and other personal protective equipment (PPE) made from such fabrics <a href="https://phys.org/news/2020-04-mask-material-virus-size-nanoparticles.html">can also be</a> washed and reused, and are more breathable.</p>
<figure class="align-center ">
<img alt="Close-up of intricately woven fibres." src="https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/356749/original/file-20200907-18-1q0r6kr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">New fabrics made from coated nanofibres could produce better PPE.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/blue-3d-texturised-technological-seamless-breathing-1074160988">AnnaVel/Shutterstock</a></span>
</figcaption>
</figure>
<p>Another important nanomaterial is
<a href="https://pubs.acs.org/doi/10.1021/acsnano.0c03697">graphene</a>, which is formed from a single honeycomb layer of carbon atoms and is <a href="https://newscenter.lbl.gov/2016/02/08/graphene-is-strong-but-is-it-tough/">200 times stronger</a> than steel but lighter than paper. Fabrics laced with graphene can capture viruses and <a href="https://pubmed.ncbi.nlm.nih.gov/28266670/">block them</a> from passing through. PPE containing graphene could be more <a href="https://onlinelibrary.wiley.com/doi/full/10.1002/admi.201900622">puncture, flame, UV and microbe resistant</a> while also being light weight. </p>
<p>Graphene isn’t reserved for fabrics either. Nanoparticles could be placed on surfaces <a href="https://www.sciencedirect.com/science/article/pii/S266608652030014X?via%253Dihub">in public places</a> that might be particularly likely to facilitate transmission of the virus.</p>
<p>These technologies are just some of the ways nanoscience is contributing to the battle against COVID-19. While there is no one answer to a global pandemic, these tiny technologies certainly have the potential to be an important part of the solution.</p><img src="https://counter.theconversation.com/content/145140/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Josh Davies-Jones does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Nanotechnology has an impressive record against viruses.Josh Davies-Jones, PhD Candidate in Chemistry, Cardiff UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1012622018-08-16T13:50:58Z2018-08-16T13:50:58ZNanomedicine could revolutionise the way we treat TB. Here’s how<figure><img src="https://images.theconversation.com/files/231068/original/file-20180808-191031-1xzxvyv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanomedicine could scupper the need for TB patients to take multiple daily tablets with toxic side effects.</span> <span class="attribution"><span class="source">Daniel Irungu/EPA</span></span></figcaption></figure><p>Tuberculosis is one of the world’s <a href="http://www.who.int/news-room/fact-sheets/detail/tuberculosis">deadliest infectious disease</a>. Worldwide, there are still about 10.4 million cases of TB and 1.7 million deaths every year. </p>
<p>One of the reasons it’s been hard to bring the disease under control is that the drugs used to treat it require a gruelling regimen and can be toxic. This means people very often don’t finish the course.</p>
<p>TB treatment lasts for six months and uses a combination of four antimicrobial drugs taken in large, daily amounts. The reason for the large daily dose is that these drugs are poorly absorbed; even when a drug gets to the infected site, only a portion of it will enter the affected tissue and fight the bacteria. They are also quickly eliminated from sites of infection by metabolic body functions.</p>
<p>These medicines also exhibit considerable toxicity such as liver damage, painful tingling in the hands and feet as well as joint pain. That’s because they don’t just target the infected areas of the body. </p>
<p>In some instances, the medicines are only available as injectables into the muscle, which is a painful procedure – and require daily clinic or prolonged hospital stays. </p>
<p>All of this leads to <a href="http://www.who.int/bulletin/volumes/85/5/06-035568/en/">poor adherence</a> to treatment among TB patients – and, ultimately, contributes to the generation and transmission of drug resistant TB strains. These are even harder to treat, with treatment lasting up to two years.</p>
<p>But there may be hope for TB treatment, in the form of <a href="https://cnm-hopkins.org/what-is-nanomedicine/">nanomedicine</a>. Tests are already being done on animals. And we are just two of many researchers from around the globe doing <a href="https://www.researchgate.net/publication/315416823_The_nanomedicine_landscape_of_South_Africa">research</a> at the nexus of nanomedicine and TB at the University of the Western Cape. </p>
<h2>How nanomedicine works</h2>
<p>Nanomedicine is the use of nanotechnology to either diagnose or treat a disease. Nanotechnology, simply put, is the creation of structures which are in the nanometer size range. One nanometer is equivalent to the diameter of a strand of human hair that has been divided ten thousand times. Human DNA is about 2.5 nanometers in diameter. Advances in science now enable scientists to engineer these tiny structures and load them with TB drugs to deliver them to infected sites in the human body.</p>
<p>Nanoparticles can be loaded with a variety of types of drugs such as proteins, DNA or even extracts from plants. Multiple drugs can be loaded in a single nanoparticle or a mixture of nanoparticles, each containing a single type of drug, can be administered. Nanomedicines can be administered into the human body through swallowing, inhaling, injections or via the skin. </p>
<p>Nanomedicines are already being used by patients for the treatment <a href="https://www.etp-nanomedicine.eu/public/about-nanomedicine/nanomedicine-applications/nanomedicine-in-cancer">of cancer</a>; examples include Doxil® and Abraxane®. Another nanomedicine, Diprivan®, is used as an anaesthetic.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/27108703">Researchers believe</a> that nanomedicine could help TB patients enormously. They would need to take less medication for a shorter duration, with fewer side effects. And, hopefully, the drugs will be cheaper. There are already <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628743/">animal trials</a> <a href="http://aac.asm.org/content/49/10/4335.short">underway</a> to test these hypotheses.</p>
<p>Our ongoing <a href="https://www.researchgate.net/publication/315416823_The_nanomedicine_landscape_of_South_Africa">research</a> focuses on the application of nanoparticles to target cells of the immune system known as macrophages. These are a major harbour for the bacteria that causes TB; <em>Mycobacterium tuberculosis</em>.</p>
<p><em>Mycobacterium tuberculosis</em> is able to multiply within the macrophages and escape elimination by the body’s immune system. Nanoparticles can be used to deliver immune-modulating signals to macrophages to turn these harbour sites into hostile environments for <em>Mycobacterium tuberculosis</em>.</p>
<p>This form of immunotherapy holds great promise: it could prevent the generation of drug resistant TB strains, since the body’s own immune system is used to kill the bacteria.</p>
<h2>Targeting TB</h2>
<p>The reason that nanoparticles hold such hope for TB treatment is that they can be carefully targeted. That’s because nanoparticles are able to make the drugs more available at the sites of infection by protecting them from breakdown prior to reaching the site. And there’s a greater uptake of the nanoparticles into infected sites. </p>
<p>Nanoparticles can also be localised to only the sites of infection. This can be achieved in two ways. First, scientists can attach chemicals to the nanoparticles’ surfaces which serve as “homing devices” and target them to desired sites. Second, nanomedicines can be inhaled so they’re localised in the lungs – the centre of TB infection.</p>
<p>The TB drugs, then, would only act at the necessary sites. Less medicine would be needed and toxic side effects would be reduced.</p>
<p>In addition, nanoparticles can control the rate at which the drug is released, extending the duration of the drug within the sites of infection. This would have significant implications for TB patients who have to take numerous drugs daily for long periods of time. Under these circumstances, more patients <a href="https://researchspace.csir.co.za/dspace/handle/10204/6486">are likely</a> to complete their courses, reducing the occurrence of drug resistance. </p>
<p>It’s hoped that these TB-specific nanomedicines will make it to human trials over the next few years, prove to be safe and effective – and start doing the important work of tackling this debilitating disease.</p><img src="https://counter.theconversation.com/content/101262/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>ADMIRE DUBE receives funding from the Fogarty International Center of the National Institutes of Health under Award Number K43TW010371. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.</span></em></p><p class="fine-print"><em><span>Sarah D'Souza does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The reason that nanoparticles hold such hope for TB treatment is that they can be carefully targeted.Sarah D'Souza, Postdoctoral Fellow in the Tuberculosis Nanomedicine Research Group, University of the Western CapeAdmire Dube, Associate Professor, Pharmaceutical Sciences, University of the Western CapeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/907402018-02-27T23:17:43Z2018-02-27T23:17:43ZHow mathematics is helping to fight cancer<figure><img src="https://images.theconversation.com/files/208167/original/file-20180227-36683-1ra49co.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Collaborations between mathematicians, cancer biologists and clinical oncologists enable both rapid cost-effective testing of cancer drug combinations, and deeper understanding of cancer drug resistance. </span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Nearly half of Canadians will develop cancer in their lifetime, <a href="http://www.cancer.ca/statistics">according to the Canadian Cancer Society</a>. Globally, <a href="http://www.who.int/mediacentre/factsheets/fs297/en/">cancer is the second leading cause of death</a>. </p>
<p>When cancer emerges in the human body, it results in cells that are “aggressive” and able to evade the body’s growth control mechanisms. These cells are also “invasive,” entering and subsuming adjacent tissues. And they are often “metastatic” — travelling to and colonizing distant sites in the body. </p>
<p>One of the greatest unsolved challenges in cancer treatment concerns the frequent relapse of patients being treated by chemotherapy, and the emergence of chemotherapeutic resistance in cancers. </p>
<p>At the <a href="http://math.uwaterloo.ca/%7Ekohandel/">Mathematical Medicine Group</a> at the University of Waterloo, we have been applying mathematical and computational approaches to understand cancer growth and control for more than a decade now. Working together with cancer biologists and clinical oncologists, we try to understand some of the challenges in cancer treatment, including drug resistance and relapse.</p>
<p>Mathematical models allow us to quickly search and identify the most effective drug combinations for cancer patients. They are also deepening our understanding of how and why cancer cells often become resistant to chemotherapy drugs.</p>
<p>We believe that this growing interaction of mathematical scientists with cancer biologists and clinical oncologists will also lead to many future advances and breakthroughs in cancer treatment.</p>
<h2>The challenge of drug resistance</h2>
<p>The standard treatment for most cancers involves a combination of surgery and chemotherapy and/or radiation therapy. </p>
<p>Chemotherapy drugs have, by and large, proved effective in destroying cancer cells by preventing them from growing and dividing. But they are clearly a “double-edged” sword as they destroy, and cause mutations in, healthy, normal tissue cells. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/205848/original/file-20180211-51727-q4eyta.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Mohammad Kohandel and PhD candidate Moriah Pellowe evaluate breast cancer cells at the Mathematical Medicine Laboratory, University of Waterloo.</span>
<span class="attribution"><span class="license">Author provided</span></span>
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</figure>
<p>And patient survival doesn’t just depend on eliminating cancer cells. We also need to control or overcome drug resistance. Every year thousands of patients die from recurrent cancers that have become resistant to chemotherapy. </p>
<p>Combination therapy is one very promising strategy. But this raises its own questions — about how to administer the drugs, which can be combined in a seemingly infinite order and sequence. </p>
<p>Mathematical models can be used to study these types of questions, offering the cancer biologist and clinical oncologist powerful new tools to add to their arsenal of laboratory and clinical approaches. </p>
<p>These models offer a rational and unique method of searching through a large number of possible strategies to identify the most efficient doses to extend patient survival. </p>
<h2>Chemotherapy itself causes resistance</h2>
<p>Our team is currently focused on developing a deeper understanding of how cancer cells become resistant to chemotherapy drugs, leading to relapse.</p>
<p>By integrating math with computational and experimental studies, we try to understand and unravel how particular combinations of drugs can help to overcome this resistance.</p>
<p>Not all cancer cells are born equal. They compete with each other and the ones that survive pass on genetic information to their daughter cells. </p>
<p>The lack of uniform characteristics among cellular populations has been identified as an important factor which complicates and impedes treatment response in a number of tumours. We have two competing theories to explain this: 1) the standard theory of “clonal evolution” and 2) the “cancer stem cell hypothesis.” </p>
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<img alt="" src="https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=389&fit=crop&dpr=1 600w, https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=389&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=389&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=489&fit=crop&dpr=1 754w, https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=489&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/208169/original/file-20180227-36686-w55bde.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=489&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Image of a cancer cell, created using 3D software.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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<p>The theory of clonal evolution states that most tumours arise from single cells through the accumulation of many genetic changes. </p>
<p>However, the cancer stem cell hypothesis suggests that only a sub-population of so-called “cancer-initiating cells” have the capacity for unlimited cell division and therefore drive tumour growth. These cells are very aggressive, less sensitive to drugs and appear to be the driving force of metastasis (the spread of cancer cells to distant sites) which frequently results in patient death.</p>
<p>Our team has published papers in <em><a href="http://www.nature.com/articles/ncomms7139">Nature Communication</a></em> and <a href="https://pubs.acs.org/doi/abs/10.1021/acsnano.6b00320"><em>ACS Nano</em></a>, in collaboration with two cancer biologists at Harvard Medical School — <a href="http://shiladitlab.com">Dr. Sengupta</a> and <a href="http://goldman.bwh.harvard.edu/">Dr. Goldman</a> — to show that non-cancer stem cells can also become resistant to chemotherapy drugs.</p>
<p>This means that resistance can be acquired as a direct result of chemotherapy. It challenges the current explanation that resistance is innate or acquired as a result of random mutations.</p>
<h2>Inspiring nanomedicine</h2>
<p>We have also used mathematical modelling, integrated with experimental data, to understand the chemo-resistant characteristics of cancer cells and how they survive treatment over time.</p>
<p>Using mouse models of aggressive breast cancer, we have confirmed the predictions from our mathematical model that, to overcome resistance and relapse, a lethal combination of drugs in a single nanoparticle (a tiny particle) must be delivered to the same cell. </p>
<p>These recent papers highlight the importance of mathematicians and cancer biologists working together. They show math can help understand cancer and also have a profound impact on therapy outcomes. </p>
<p>Mathematical and computational strategies provide a painless, fast and cost-effective way of testing different drug combination strategies, as well as other hypotheses using computational models.</p>
<p>Math can even inspire the design of nanomedicine!</p><img src="https://counter.theconversation.com/content/90740/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mohammad Kohandel receives funding from the Natural Sciences and Engineering Research Council of Canada (NSERC).</span></em></p>Cancer is the second leading cause of death globally. Mathematicians have joined the fight, developing models to both test cancer drug combinations and understand chemotherapy drug resistance.Mohammad Kohandel, Associate Professor of Applied Mathematics, University of WaterlooLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/698972017-05-23T04:31:56Z2017-05-23T04:31:56ZExplainer: what is nanomedicine and how can it improve childhood cancer treatment?<figure><img src="https://images.theconversation.com/files/162310/original/image-20170324-4934-1axxk5x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Therapies on a nano scale rely on engineered nanoparticles designed to package and deliver drugs to exactly where they’re needed.</span> <span class="attribution"><span class="source">from shutterstock.com</span></span></figcaption></figure><p>A recent <a href="http://www.cancerresearchuk.org/about-us/cancer-news/news-report/2016-11-08-childhood-cancer-survivors-live-longer-but-not-necessarily-with-better-health">US study of people treated for cancer as children</a> from the 1970s to 1999 showed that although survival rates have improved over the years, the quality of life for survivors is low. It also showed this was worse for those who were treated in the 1990s.</p>
<p>About 70% of childhood cancer survivors experience side effects from their treatment, including secondary cancers. And as survival rates improve, the worldwide population of childhood cancer survivors is growing. </p>
<p>Side effects cause stress for survivors and families and increase demand on health systems. But an emerging area of medicine, nanomedicine, offers hope for better children’s cancer treatment that will have fewer side effects and improve quality of life for survivors.</p>
<h2>What is nanomedicine?</h2>
<p>Nanomedicine is the application of nanomaterials, or nanoparticles, to medicine. Nanoparticles are a form of transport for drugs and can go places drugs wouldn’t be able to go on their own.</p>
<p>Nano means tiny. A nanometre (nm) is one-billionth of a metre. Nanoparticles used for drug delivery are usually in the 20 to 100 nanometre range, although this can vary depending on the design of the nanoparticle.</p>
<p>Nanoparticles can be engineered and designed to package and transport drugs directly to where they’re needed. This targeted approach means the drugs cause most harm in the particular, and intended, area of the tumour they are delivered to. This minimises collateral damage to surrounding healthy tissues, and therefore the side effects.</p>
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<img alt="" src="https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=353&fit=crop&dpr=1 600w, https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=353&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=353&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=443&fit=crop&dpr=1 754w, https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=443&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/162126/original/image-20170323-25748-1yxkn21.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=443&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="attribution"><a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>The first cancer nanomedicine approved by the US Food and Drug Administration was
<a href="http://www.sciencedirect.com/science/article/pii/S0169409X16301351">Doxil</a>. Since 1995, it has been used to treat adult cancers including ovarian cancer, multiple myeloma and Karposi’s sarcoma (a rare cancer that often affects people with immune deficiency such as HIV and AIDS).</p>
<p>Currently, there is <a href="http://www.sciencedirect.com/science/article/pii/S0169409X16301351">a stream of new nanomedicine treatments</a> for adult cancers in clinical trials (trials in humans), or on the market. But only a limited number of these have been approved for children’s cancers, although this is arguably where nanomedicine’s strengths could have the most benefit. </p>
<h2>How does nanomedicine work?</h2>
<p>The nanoparticle drug-delivery systems can work in different ways. Along with carrying the drug for delivery, nanoparticles can be engineered to carry specific compounds that will let them bind, or attach, to molecules on tumour cells. Once attached, they can safety deliver the drug to the specific tumour site.</p>
<p>Nanoparticles can also help with drug solubility. For a drug to work, it must be able to enter the bloodstream, which means it needs to be soluble. For example, the cancer drug paclitaxel (Taxol) is insoluble so has to be dissolved in a delivery agent to get into the blood. But this agent can <a href="https://www.ncbi.nlm.nih.gov/pubmed/24740483">cause allergic reactions</a> in patients. </p>
<p>To overcome these issues, <a href="https://www.ncbi.nlm.nih.gov/pubmed/16722814">chemists have developed</a> a nanoparticle out of the naturally occurring protein albumin. It carries the paclitaxel and makes it soluble but without the allergic reactions.</p>
<p>Tumours commonly have disordered and leaky blood vessels sprouting through and off them. These vessels allow chemotherapy drugs to readily enter the tumour, but because chemotherapy molecules are so small, they also diffuse through the vessels and out of the tumour, attacking surrounding tissues. Nanoparticles are larger molecules that get trapped inside the tumour, where they do all the damage.</p>
<p>Once they have delivered their drug cargo to cells, nanoparticles can be designed to break down into harmless byproducts. This is particularly important for children who are still developing. </p>
<h2>Types of nanoparticles</h2>
<p>Nanoparticles vary in characteristics like shape and size. Researchers need to match the right nanoparticle to the drug it’s to deliver and the particular tumour.</p>
<p>An array of nanoparticle structures are currently being engineered. One example of an interesting structure is the shape of a DNA origami. Because DNA is a biological material, nanoparticles engineered into DNA origami shapes won’t be seen as foreign by the immune system. So these can transport a drug to diseased cells while evading the body’s immune system, therefore lessening the side effects of drugs. </p>
<p>Another example of nanomedicine structures are polymeric nanocarriers. We have recently identified a gene that promotes the growth of tumours, cancer spread and resistance to chemotherapy in pancreatic cancers. </p>
<p>We used a <a href="https://www.ncbi.nlm.nih.gov/pubmed/27305597">nanomedicine called a polymeric nanocarrier</a> and combined it with a drug that silences the cancer gene. We <a href="https://newsroom.unsw.edu.au/news/health/new-cancer-nanomedicine-reduces-pancreatic-tumour-growth">packaged this up to form a nanomedicine and delivered the drugs</a> into the tumour. </p>
<p>These nanomedicines reduced the expression of the cancer gene, blocked tumour growth and reduced the spread of pancreatic cancer. But we also showed that polymeric nanocarriers can be combined in the lab with other gene-silencing drugs. This means the method can be used for a range of other gene-based cancers.</p>
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<span class="attribution"><span class="source">The Conversation</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<hr>
<h2>How can nanomedicines help treat kids’ cancer?</h2>
<p>In standard treatment for children’s cancer, chemotherapy drugs are often prescribed at the maximum tolerable dose for a child’s age or size, based on adult dosages. But children aren’t small adults. The processes underlying children’s growth and development might lead to a different effect and response to a chemotherapy drug not seen in adults.</p>
<p>Also, if a child becomes resistant to a drug and they’re on the maximum tolerable dose, there’s no scope to increase it without toxic side effects. By packaging up drugs and moving them through the body directly to diseased cells to reduce collateral damage, in theory, nanomedicine allows higher doses of drugs to be used.</p>
<p>Nanomedicine has great potential to safely treat children’s cancer. However, it is currently stymied by <a href="http://austinpublishinggroup.com/material-science-engineering/fulltext/amse-v1-id1006.php">too little research</a>. About <a href="https://www.ncbi.nlm.nih.gov/pubmed/22684017">two-thirds of research attention</a> in nanomedicine therapeutics, of more 250 nanomedicine products, is focused on cancer. Yet this isn’t translating into new cancer treatments for children coming to market.</p>
<p>But we are making progress. Our work is exploring the design of nanoparticles to deliver gene-silencing drugs to treat the most common brain cancer in children – medulloblastoma. </p>
<p>We’re also working on nanomedicines for other significant childhood cancers. These include drug-refractory acute lymphoblastic leukaemia, the most common childhood cancer, and neuroblastoma, the cancer that claims more lives of those under five than any other.</p><img src="https://counter.theconversation.com/content/69897/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maria Kavallaris receives funding from the National Health and Medical Research Council, Australian Research Council, Cancer Council NSW, and The Kids Cancer Project.</span></em></p><p class="fine-print"><em><span>Thomas P Davis receives funding from the Australian Research Council and the National Health and Medical Research Council</span></em></p><p class="fine-print"><em><span>Joshua McCarroll does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Nanoparticles are a form of transport for drugs and can go places drugs wouldn’t be able to go on their own. They make drug delivery more targeted, reducing collateral damage to healthy tissues.Maria Kavallaris, Professor, Children's Cancer InstituteJoshua McCarroll, Project Leader, Children's Cancer Institute and Senior Lecturer, Medicine, UNSW SydneyThomas P Davis, ARC Laureate Fellow, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/552542016-03-22T11:23:55Z2016-03-22T11:23:55ZFive ways nanotechnology is securing your future<figure><img src="https://images.theconversation.com/files/115999/original/image-20160322-32283-1f9sla3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hidden tools are making the world a safer place</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The past 70 years have seen the way we live and work transformed by two tiny inventions. The electronic transistor and the microchip are what make all modern electronics possible, and since their development in the 1940s they’ve been getting smaller. Today, one chip can contain as many as <a href="http://www.extremetech.com/extreme/187612-ibm-cracks-open-a-new-era-of-computing-with-brain-like-chip-4096-cores-1-million-neurons-5-4-billion-transistors">5 billion transistors</a>. If cars had followed the same development pathway, we would now be able to drive them at <a href="http://www.cyrrusanalytics.com/#!The-300000-MPH-Volkswagen/cudg/561206a00cf25fa7fe26bc95">300,000mph</a> and they would cost just £3 each. </p>
<p>But to keep this progress going we need to be able to create circuits on the extremely small, nanometre scale. A nanometre (nm) is one billionth of a metre and so this kind of engineering involves <a href="http://mashable.com/2013/05/01/ibm-atomic-movie/#mI9MdlKo9uq5">manipulating individual atoms</a>. We can do this, for example, by firing a <a href="http://www.sciencedirect.com/science/article/pii/S0169433200003524">beam of electrons</a> at a material, or by vaporising it and depositing the resulting gaseous atoms <a href="http://www.sciencedirect.com/science/article/pii/S1369702114001436">layer by layer</a> onto a base.</p>
<p>The real challenge is using such techniques reliably to manufacture working nanoscale devices. The physical properties of matter, such as its melting point, electrical conductivity and chemical reactivity, become very different at the nanoscale, so shrinking a device can <a href="http://www.nano.gov/nanotech-101/special">affect its performance</a>. If we can master this technology, however, then we have the opportunity to improve not just electronics but all sorts of areas of modern life.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=393&fit=crop&dpr=1 600w, https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=393&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=393&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=494&fit=crop&dpr=1 754w, https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=494&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/115989/original/image-20160322-32309-1gvd1se.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=494&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Medical nanobots.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>1. Doctors inside your body</h2>
<p>Wearable fitness technology means we can monitor our health by strapping gadgets to ourselves. There are even prototype electronic tattoos that can <a href="http://www.wired.com/2013/03/sensor-tattoos/">sense our vital signs</a>. But by scaling down this technology, we could go further by implanting or injecting tiny sensors inside our bodies. This would capture much more detailed information with less hassle to the patient, enabling doctors to personalise their treatment.</p>
<p>The possibilities are endless, ranging from monitoring inflammation and post-surgery recovery to more exotic applications whereby electronic devices actually interfere with our body’s signals for controlling organ function. Although these technologies might sound like a thing of the far future, multi-billion healthcare firms <a href="http://www.cnbc.com/2015/03/11/glaxosmithklines-big-bet-on-electroceuticals.html">such as GlaxoSmithKline</a> are already working on ways to develop so-called “electroceuticals”.</p>
<h2>2. Sensors, sensors, everywhere</h2>
<p>These sensors rely on newly-invented <a href="http://www.azonano.com/article.aspx?ArticleID=4152">nanomaterials and manufacturing techniques</a> to make them smaller, more complex and more energy efficient. For example, sensors with very fine features can now be printed in large quantities on flexible rolls of plastic at low cost. This opens up the possibility of placing sensors at lots of points over <a href="http://www.rh.gatech.edu/news/206881/wireless-smart-skin-sensors-could-provide-remote-monitoring-infrastructure">critical infrastructure</a> to constantly check that everything is running correctly. Bridges, aircraft and even nuclear power plants could benefit.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/115992/original/image-20160322-32323-xbcrq5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Worried about your hairline?</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>3. Self-healing structures</h2>
<p>If cracks do appear then nanotechnology could play a further role. Changing the structure of materials at the nanoscale can give them some amazing properties – by giving them a texture <a href="http://edition.cnn.com/2013/01/17/tech/mobile/p2i-liquid-repellent-nano-coating/">that repels water</a>, for example. In the future, nanotechnology coatings or additives will even have the potential to allow materials to “heal” when damaged or worn. For example, dispersing nanoparticles throughout a material means that they can migrate to fill in any cracks that appear. This could produce self-healing materials for everything from <a href="http://phys.org/news/2006-02-nano-world-self-healing-material.html">aircraft cockpits to microelectronics</a>, preventing small fractures from turning into large, more problematic cracks.</p>
<h2>4. Making big data possible</h2>
<p>All these sensors will produce more information than we’ve ever had to deal with before – so we’ll need the technology to process it and <a href="http://www.forbes.com/sites/ciocentral/2012/07/05/best-practices-for-managing-big-data/#275083feef02">spot the patterns</a> that will alert us to problems. The same will be true if we want to use the “<a href="https://theconversation.com/explainer-what-is-big-data-13780">big data</a>” from traffic sensors to help <a href="https://theconversation.com/how-big-data-and-the-sims-are-helping-us-to-build-the-cities-of-the-future-47292">manage congestion</a> and prevent accidents, or <a href="https://theconversation.com/the-promise-and-perils-of-predictive-policing-based-on-big-data-48366">prevent crime</a> by using statistics to more effectively allocate police resources.</p>
<p>Here, nanotechnology is helping to create <a href="https://www.theengineer.co.uk/nanostructured-glass-used-for-high-density-5d-data-storage/">ultra-dense memory</a> that will allow us to store this wealth of data. But it’s also providing the inspiration for ultra-efficient algorithms for processing, encrypting and communicating data without compromising its reliability. Nature has several examples of big-data processes efficiently being performed in real-time by tiny structures, such as the parts of <a href="https://www.technologyreview.com/s/522476/thinking-in-silicon/">the eye and ear</a> that turn external signals into information for the brain. </p>
<p>Computer architectures <a href="http://blogs.scientificamerican.com/observations/brain-inspired-computing-reaches-a-new-milestone/">inspired by the brain</a> could also use energy more efficiently and so would struggle less with excess heat – one of the key problems with shrinking electronic devices further.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/115995/original/image-20160322-32283-1x11t7u.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">From nano tech to global warming.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>5. Tackling climate change</h2>
<p>The fight against climate change means we need new ways to generate and use electricity, and nanotechnology is already playing a role. It has helped create <a href="https://theconversation.com/lithium-air-a-battery-breakthrough-explained-50027">batteries that can store more energy</a> for electric cars and has enabled <a href="http://www.nanowerk.com/nanotechnology-news/newsid=37903.php">solar panels to convert more sunlight into electricity</a>. </p>
<p>The common trick in both applications is to <a href="http://www.telegraph.co.uk/news/science/science-news/12174733/Smart-wallpaper-which-absorbs-light-could-help-power-home.html">use nanotexturing</a> or nanomaterials (for example nanowires or carbon nanotubes) that turn a flat surface into a three-dimensional one with a much greater surface area. This means that there is more space for the reactions that enable energy storage or generation to take place, so the devices operate more efficiently</p>
<p>In the future, nanotechnology could also enable objects to harvest energy from their environment. New nano-materials and concepts are currently being developed that show potential for producing <a href="http://www.nanowerk.com/spotlight/spotid=33308.php">energy from movement</a>, light, variations in temperature, glucose and other sources with high conversion efficiency.</p><img src="https://counter.theconversation.com/content/55254/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Themis Prodromakis receives funding from the Lloyds Register Foundation, the EPSRC and the EU Commission. </span></em></p>From tiny robotic doctors repairing your body to the latest climate change-tackling tools, nanotechnology is fighting an invisible battle on our behalf.Themis Prodromakis, Reader in Nanoelectronics, University of SouthamptonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/422012015-05-22T14:11:48Z2015-05-22T14:11:48ZUltrasound-activated bubbles could help make cancer drugs more effective and less nasty<figure><img src="https://images.theconversation.com/files/82558/original/image-20150521-985-1gxrao3.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Nanoparticles: small but deadly... to cancer</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Despite extraordinary advances in new drugs and biotechnology, cancer is still one of the leading causes of death worldwide.</p>
<p>In many cases, the problem lies not with the drugs but rather the difficulty in successfully delivering them to the site of a tumour. In healthy tissue there is a regular structure of blood vessels supplying oxygen and nutrients to cells, which divide and grow at a steady rate. In cancerous tumours, however, cells divide and grow in an unregulated way, producing a <a href="http://www.ncbi.nlm.nih.gov/pubmed/2292138">chaotic vessel structure</a> and regions of tissue with little or no blood supply.</p>
<p>This means when drugs are ingested or injected into the blood stream, they don’t reach all parts of the tumour and there is a high risk of cancer recurring after treatment. On top of this, the <a href="http://www.ncbi.nlm.nih.gov/pubmed/9018236">pressure inside</a> many tumours prevents a drug from being absorbed from the blood, meaning only a very small fraction of it is actually delivered. The rest of the drug circulates around the body and is eventually absorbed by healthy tissue, often leading to intolerable side effects.</p>
<p>One of the major goals of the research being carried out in the <a href="http://www.ibme.ox.ac.uk">Oxford Institute of Biomedical Engineering</a> (IBME) is to develop new methods for delivering anti-cancer drugs that overcome these barriers. While engineers are perhaps more commonly thought of in the context of large construction projects, we are using precisely the same combination of applied science and problem solving.</p>
<h2>Building nanoparticles</h2>
<p>There is a formidable series of challenges to address to solve this problem. First, we need to encapsulate the drug to prevent it from interacting with healthy tissue and/or deactivating before reaching the tumour. Second, we need a way to deliver the drug to the tumour to maximise the concentration it receives.</p>
<p>Third, we need a mechanism for releasing the drug on demand once it has built up within the tumour. Fourth, we need to ensure the released drug is evenly spread throughout the tumour. And finally, we need to be able to monitor the treatment from outside the body.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/82570/original/image-20150521-995-s69931.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Taking the fight to cancer.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Our team at the IBME has developed a range of new techniques for creating tiny particles into which we can insert drugs with a high degree of precision. And we have tried a <a href="http://www.ncbi.nlm.nih.gov/pubmed/18261822">variety of methods</a> to make the particles release the drug. These include using materials that are sensitive to the pH change within a tumour and materials that break down upon heating or undergo a phase change (from a solid to a liquid or liquid to a gas).</p>
<p>But one of the most versatile means of triggering drug release is by firing a beam of <a href="http://www.ncbi.nlm.nih.gov/pubmed/23121385">ultrasonic vibrations</a> at the particles. Widely used as an <a href="http://www.nhs.uk/conditions/ultrasound-scan/pages/introduction.aspx">imaging method</a>, ultrasound can be used from outside the body and, unlike light or heat, can be tightly focused to produce highly localised effects.</p>
<p>In order to produce particles that respond to ultrasound, we have to include in them a gas or a liquid that easily vaporises. When exposed to the ultrasound, the gas/liquid will undergo a rapid expansion and force the drug out of the particle.</p>
<h2>Ultrasound activated bubbles</h2>
<p>This process generates a pulsating gas or vapour bubble that has several other significant benefits for drug delivery. The motion of the bubble produced by the ultrasound field helps to drive the drug out of the blood vessels and deep into the surrounding tumour. We have shown that bubbles can push drugs <a href="http://www.ibme.ox.ac.uk/research/non-invasive-therapy-drug-delivery/enhanced-drug-delivery">up to four times deeper</a> into tissue than they would normally diffuse, sufficient to achieve a uniform spread throughout a tumour.</p>
<p>There is also a growing body of research that shows microbubbles and ultrasound make cancer cells more permeable to drugs, speeding up the rate at which they work and ultimately cell death. The microbubbles’ motion produces a secondary ultrasound signal that can be detected outside the body. This means the location and activity of the particles can be <a href="http://www.ncbi.nlm.nih.gov/pubmed/25564961">continuously monitored</a>, providing real-time feedback on the progress of the treatment.</p>
<p>Our aim over the next five years is to translate these developments into clinical use. The work will focus on improving the delivery of four classes of drug that have shown enormous potential but that currently struggle to get inside a tumour and/or have unacceptable side effects. By combining our expertise in encapsulation with the use of ultrasound and shockwaves, we hope to create more effective drugs that can be delivered straight to the location of a tumour and monitored with advanced imaging techniques.</p>
<p><em>This article is adapted from the 2015 IET A. F. Harvey Prize Lecture</em></p><img src="https://counter.theconversation.com/content/42201/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Eleanor Stride is a non-executive director of AtoCap Ltd. She receives funding from the Engineering and Physical Sciences Research Council, Cancer Research UK, Multiple Scelerosis Society.</span></em></p>New research could into nanoparticles could help deliver drugs straight to the site of tumours and make them more effective when they get there.Eleanor Stride, Professor of Engineering Science, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/317152014-09-18T05:28:15Z2014-09-18T05:28:15ZNew device uses nano-magnets to cleanse bad blood when sepsis strikes<figure><img src="https://images.theconversation.com/files/59301/original/44b32sw6-1410954682.jpg?ixlib=rb-1.1.0&rect=34%2C188%2C971%2C740&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Clean up act.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/denn/4311117490/sizes/o/in/photolist-7yXB2U-ab6DAy-dX2TzK-4AUY2j-dTnLJx-oyvv9M-4sUZTC-eE9WzD-6Nvp2-7KZrSc-9BAAXQ-bE9kx4-bE9jtV-aRMCGH-aRMCfc-aRMCKe-aRMCDr-oeCD64-oeQ5gx-bE9kVB-breorY-bE9i7T-bE9jPP-brermu-bE9iRr-owhYxX-ovGocu-oetWVa-owmcGB-oeCCep-ovU9aC-ou1P65-oeYDvy-dwZFit-otQyRo-oeShPK-oemA7S-oetzCc-ovEuXh-oeZjyL-oeye3W-oenRfW-owsJ1N-ovWwbf-oyewRD-oeUmYT-ovS4zF-aRMChM-aRMCkH-aRMCjn-aRMCgz/">Denn</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Sepsis claims the lives of 8m people worldwide each year. It is <a href="http://kdvr.com/2014/09/15/sepsis-little-known-illness-that-is-leading-cause-of-hospital-deaths-in-u-s/">the leading cause</a> of hospital deaths in the US, a major threat to soldiers wounded in battle and a killer of children, particularly in under-resourced areas around the world.</p>
<p><a href="http://www.mayoclinic.org/diseases-conditions/sepsis/basics/definition/con-20031900">Sepsis</a> occurs when bacteria, fungi or viruses multiply in a patient’s blood and trigger a chain reaction that causes inflammation, blood clotting, and organ damage. Traditional treatment requires doctors to race against the clock to pinpoint the specific type of pathogen causing the infection so that the right antibiotic therapy can be administered. But in many cases blood cultures never make a positive identification, so we often treat them blindly. </p>
<p>Patients generally receive broad-spectrum antibiotics along the way, but things <a href="http://www.nhs.uk/Conditions/Blood-poisoning/Pages/Treatment.aspx">often go downhill fast</a> and can end in septic shock, where blood pressure drops to dangerous levels. This is a challenge made greater still by the growing population of antibiotic-resistant superbugs and viruses where we currently have no treatment at all.</p>
<p>But there is some hope. Here at <a href="http://wyss.harvard.edu/viewpage/about-us/about-us">Harvard’s Wyss Institute</a>, we are hot on the trail of the sepsis problem. In collaboration with other Harvard colleagues and two hospitals, we’ve developed a dialysis-like therapeutic device that could radically transform the way doctors treat sepsis, which we <a href="http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3640.html">announced in Nature Medicine</a>.</p>
<h2>Meet ‘the biospleen’</h2>
<p>The “biospleen” is a device inspired by the human spleen, <a href="http://www.webmd.com/digestive-disorders/picture-of-the-spleen">which filters pathogens and toxins</a> from flowing blood without requiring doctors to identify the pathogen causing the problem – and it captures antibiotic-resistant bacteria as well. We found that it was able to remove more than 90% of bacteria from the blood of rats in a few hours. It also increased survival when these animals were injected with a lethal bacterial toxin. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=207&fit=crop&dpr=1 600w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=207&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=207&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=260&fit=crop&dpr=1 754w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=260&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=260&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Pathogen’s find it magnetic.</span>
<span class="attribution"><span class="source">Harvard's Wyss Institute</span></span>
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<p>The biospleen works outside the body like a dialysis machine. It consists of two hollow channels that are connected to each other by a series of slits: one channel contains flowing blood and the other has a saline solution. Key to its success are tiny nanometer-sized magnetic beads that are coated with a genetically engineered version of a natural immune system protein called mannose binding lectin (MBL). </p>
<p>The magnetic beads are added to the blood after it flows from a patient’s vein and before it enters the device. After the beads bind to pathogens, they are pulled from the flowing blood, through the slits, and into the neighbouring saline channel by a magnet in the device, which cleans the blood before being returned to the patient. </p>
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<a href="https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=251&fit=crop&dpr=1 600w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=251&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=251&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=315&fit=crop&dpr=1 754w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=315&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=315&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Stuck on you.</span>
<span class="attribution"><span class="source">Harvard Wyss Institute</span></span>
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<p>Best of all? The device simply and effectively cleans the blood without the need to first pinpoint the pathogen responsible for the infection because the MBL protein binds to more than 90 different causes of infection and sepsis, including bacteria, fungi, viruses, parasites and toxins.</p>
<h2>Getting ideas out of the lab</h2>
<p>Very innovative and potentially groundbreaking ideas often get stuck in the mire of traditional academic laboratories because they cannot be validated to the degree required by financial investors, for example, by working through manufacturing and regulatory challenges. </p>
<p>At the Wyss Institute, we’ve teamed up in-house inventors, engineers and entrepreneurs to speed up the commercialisation of our technologies. They’ll work with the blood cleansing device to get it out of the laboratory as soon as possible to begin saving lives. </p>
<p>The major reason no-one ever explored this idea in the past is that most clinicians and researchers assume that because blood cultures are negative, there are no circulating pathogens. But the reality is that there is circulating dead pathogen debris and many toxins, which are primary triggers of the inflammatory cascade that leads to sepsis. The power of this device is that it binds to dead pathogens and toxins as well as live bugs.</p>
<p>The next step will be to test and validate the technology in large animal studies and from there into human clinical trials.</p><img src="https://counter.theconversation.com/content/31715/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Donald Ingber is founding director of the Wyss Institute for BIologically Inspired Engineering, and a professor at Harvard's schools of medicine and engineering. The biospleen was developed in collaboration with the Harvard School of Engineering and Applied Sciences, Boston Children’s Hospital, Harvard Medical School, and Massachusetts General Hospital</span></em></p>Sepsis claims the lives of 8m people worldwide each year. It is the leading cause of hospital deaths in the US, a major threat to soldiers wounded in battle and a killer of children, particularly in under-resourced…Donald Ingber, Founding Director of the Wyss Institute, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.