Precious Metal Flecks Could be Catalyst for Better Cancer Therapies


Precious Metal Flecks Cancer shutterstock_716719006

 

Researchers have found a way to dispatch minute fragments of palladium—a key component in motor manufacture, electronics and the oil industry—inside cancerous cells.

Tiny extracts of a precious metal used widely in industry could play a vital role in new cancer therapies.

Scientists have long known that the metal, used in catalytic converters to detoxify exhaust, could be used to aid cancer treatment but, until now, have been unable to deliver it to affected areas.

A molecular shuttle system that targets specific cancer cells has been created by a team at the University of Edinburgh and the Universidad de Zaragoza in Spain.

The new method, which exploits palladium’s ability to accelerate—or catalyse—chemical reactions, mimics the process some viruses use to cross cell membranes and spread infection.

The team has used bubble-like pouches that resemble the biological carriers known as exosomes, which can transport essential proteins and genetic material between cells. These exosomes exit and enter cells, dump their content, and influence how the cells behave.

This targeted transport system, which is also exploited by some viruses to spread infection to other cells and tissues, inspired the team to investigate their use as shuttles of therapeutics.

The researchers have now shown that this complex communication network can be hijacked. The team created exosomes derived from lung cancer cells and cells associated with glioma—a tumour that occurs in the brain and spinal cord—and loaded them with palladium catalysts.

These artificial exosomes act as Trojan horses, taking the catalysts—which work in tandem with an existing cancer drug- straight to primary tumours and metastatic cells.

Having proved the concept in laboratory tests, the researchers have now been granted a patent that gives them exclusive rights to trial palladium-based therapies in medicine.

The study was funded by the Engineering and Physical Sciences Research Council and the European Research Council. It has been published in the journal, Nature Catalysis.

Professor Asier Unciti-Broceta, from the University of Edinburgh’s CRUK Edinburgh Centre, said: “We have tricked exosomes naturally released by cancer cells into taking up a metal that will activate chemotherapy drugs just inside the cancer cells, which could leave healthy cells untouched.”

Professor Jesús Santamaría, of the Universidad de Zaragoza, said: “This has the potential to be a very exciting technology. It could allow us to target the main tumour and metastatic cells, thus reducing the side effects of chemotherapy without compromising the treatment.”

Story Source:

Materials provided by University of Edinburgh. Note: Content may be edited for style and length.

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Researchers Develop Nanoparticle-Based Vaccine for Skin Cancer


nanovaccine

Nano-particles developed by scientists at Tel Aviv University have proven effective to prevent and treat melanoma.

 

While scientists have made great strides over the years to treat cancer, a vaccine for the disease—which comes in many forms and with many complexities–has yet to be discovered.

Researchers at Tel Aviv University have made a breakthrough in this endeavor with the development of a nano-vaccine for the most aggressive type of melanoma—skin cancer. The vaccine—based on a novel nanoparticle—already has shown effective in preventing the development of melanoma in mice as well as in treating the initial tumors that result from the disease, researchers said.

Researchers have developed a new nano-vaccine for melanoma, the most aggressive type of skin cancer. The vaccine is the first of its kind for cancer and paves the way for promising new prevention and treatment methods for the disease, researchers said. (Image source: Tel Aviv University)

Melanoma develops in the skin cells that produce melanin or skin pigment, but then can metastasize quickly into the brain and other organs. It currently is treated in a number of ways, including chemotherapy, radiation therapy, and immunotherapy.

All of these methods attack the disease after the fact; so far, no treatment has emerged to prevent or delay its growth in the first place, Professor Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology at Tel Aviv University, said in a press statement.

“The vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” said Satchi-Fainaro, who also is head of the Laboratory for Cancer Research and Nanomedicine at the university’s Sackler Faculty of Medicine. “In our study, we have shown for the first time that it is possible to produce an effective nano-vaccine against melanoma and to sensitize the immune system to immunotherapies.”

A New Approach

Nanoparticles about 170 nanometers in size are key to the approach researchers took to developing their novel vaccine. They packed two peptides—or short chains of amino acids—into each particle, which are made of a biodegradable polymer. Peptides are present in melanoma cells.

To test their vaccine, researchers injected the nano-particles into a mouse with melanoma to test its effectiveness. What they found is that the nanoparticles acted similarly to existing vaccines for viruses, which long have proved effective against viral-borne diseases, Satchi-Fainaro said.

“They stimulated the immune system of the mice, and the immune cells learned to identify and attack cells containing the two peptides–that is, the melanoma cells,” she said in the statement. “This meant that, from now on, the immune system of the immunized mice will attack melanoma cells if and when they appear in the body.”

Researchers published a study on their work in the journal Nature Nanotechnology.

Successful Prevention and Treatment

Satchi-Fainaro’s team focused on three different conditions to determine the nano-vaccine’s effectiveness. The first was to see if it would prevent the growth of the disease if melanoma cells were injected into mice, which it did, she said.

Researchers also used the nano-vaccine to treat a primary melanoma tumor in combination with immunotherapy treatments, they said. The treatment delayed the progression of the disease and significantly extended the lives of the mice in this study, researchers said.

Finally, the researchers gauged the nano-vaccine’s effectiveness in treating brain metastases, which are associated with melanoma, using tissue from patients with these metastases. The vaccine showed it could also be a successful treatment in this case, paving the way for “effective treatment of melanoma, even in the most advanced stages of the disease,” Satchi-Fainaro said in the statement.

The team plans to continue its work to develop nano-particles to vaccinate people not only against melanoma, but potentially against other forms of cancer as well, she added.

 

MIT: Study Furthers Radically New View of Gene Control


  • MIT researchers have developed a new model of gene control, in which the cellular machinery that transcribes DNA into RNA forms specialized droplets called condensates.

  • Image: Steven H. Lee

  • Along the genome, proteins form liquid-like droplets that appear to boost the expression of particular genes.

    In recent years, MIT scientists have developed a new model for how key genes are controlled that suggests the cellular machinery that transcribes DNA into RNA forms specialized droplets called condensates. These droplets occur only at certain sites on the genome, helping to determine which genes are expressed in different types of cells.

    In a new study that supports that model, researchers at MIT and the Whitehead Institute for Biomedical Research have discovered physical interactions between proteins and with DNA that help explain why these droplets, which stimulate the transcription of nearby genes, tend to cluster along specific stretches of DNA known as super enhancers. These enhancer regions do not encode proteins but instead regulate other genes.

    “This study provides a fundamentally important new approach to deciphering how the ‘dark matter’ in our genome functions in gene control,” says Richard Young, an MIT professor of biology and member of the Whitehead Institute.

    Young is one of the senior authors of the paper, along with Phillip Sharp, an MIT Institute Professor and member of MIT’s Koch Institute for Integrative Cancer Research; and Arup K. Chakraborty, the Robert T. Haslam Professor in Chemical Engineering, a professor of physics and chemistry, and a member of MIT’s Institute for Medical Engineering and Science and the Ragon Institute of MGH, MIT, and Harvard.

    Graduate student Krishna Shrinivas and postdoc Benjamin Sabari are the lead authors of the paper, which appears in Molecular Cell on Aug. 8.

    “A biochemical factory”

    Every cell in an organism has an identical genome, but cells such as neurons or heart cells express different subsets of those genes, allowing them to carry out their specialized functions. Previous research has shown that many of these genes are located near super enhancers, which bind to proteins called transcription factors that stimulate the copying of nearby genes into RNA.

    About three years ago, Sharp, Young, and Chakraborty joined forces to try to model the interactions that occur at enhancers.

    In a 2017 Cell paper, based on computational studies, they hypothesized that in these regions, transcription factors form droplets called phase-separated condensates. Similar to droplets of oil suspended in salad dressing, these condensates are collections of molecules that form distinct cellular compartments but have no membrane separating them from the rest of the cell.

    In a 2018 Science paper, the researchers showed that these dynamic droplets do form at super enhancer locations. Made of clusters of transcription factors and other molecules, these droplets attract enzymes such as RNA polymerases that are needed to copy DNA into messenger RNA, keeping gene transcription active at specific sites.

    “We had demonstrated that the transcription machinery forms liquid-like droplets at certain regulatory regions on our genome, however we didn’t fully understand how or why these dewdrops of biological molecules only seemed to condense around specific points on our genome,” Shrinivas says.

    As one possible explanation for that site specificity, the research team hypothesized that weak interactions between intrinsically disordered regions of transcription factors and other transcriptional molecules, along with specific interactions between transcription factors and particular DNA elements, might determine whether a condensate forms at a particular stretch of DNA. Biologists have traditionally focused on “lock-and-key” style interactions between rigidly structured protein segments to explain most cellular processes, but more recent evidence suggests that weak interactions between floppy protein regions also play an important role in cell activities.

    In this study, computational modeling and experimentation revealed that the cumulative force of these weak interactions conspire together with transcription factor-DNA interactions to determine whether a condensate of transcription factors will form at a particular site on the genome. Different cell types produce different transcription factors, which bind to different enhancers. When many transcription factors cluster around the same enhancers, weak interactions between the proteins are more likely to occur. Once a critical threshold concentration is reached, condensates form.

    “Creating these local high concentrations within the crowded environment of the cell enables the right material to be in the right place at the right time to carry out the multiple steps required to activate a gene,” Sabari says. “Our current study begins to tease apart how certain regions of the genome are capable of pulling off this trick.”

    These droplets form on a timescale of seconds to minutes, and they blink in and out of existence depending on a cell’s needs.

    “It’s an on-demand biochemical factory that cells can form and dissolve, as and when they need it,” Chakraborty says. “When certain signals happen at the right locus on a gene, the condensates form, which concentrates all of the transcription molecules. Transcription happens, and when the cells are done with that task, they get rid of them.”

    “A functional condensate has to be more than the sum of its parts, and how the protein and DNA components work together is something we don’t fully understand,” says Rohit Pappu, director of the Center for Science and Engineering of Living Systems at Washington University, who was not involved in the research. “This work gets us on the road to thinking about the interplay among protein-protein, protein-DNA, and possibly DNA-DNA interactions as determinants of the outputs of condensates.”

    A new view

    Weak cooperative interactions between proteins may also play an important role in evolution, the researchers proposed in a 2018 Proceedings of the National Academy of Sciences paper.

    The sequences of intrinsically disordered regions of transcription factors need to change only a little to evolve new types of specific functionality. In contrast, evolving new specific functions via “lock-and-key” interactions requires much more significant changes.

    “If you think about how biological systems have evolved, they have been able to respond to different conditions without creating new genes.

    We don’t have any more genes that a fruit fly, yet we’re much more complex in many of our functions,” Sharp says. “The incremental expanding and contracting of these intrinsically disordered domains could explain a large part of how that evolution happens.”

    Similar condensates appear to play a variety of other roles in biological systems, offering a new way to look at how the interior of a cell is organized.

    Instead of floating through the cytoplasm and randomly bumping into other molecules, proteins involved in processes such as relaying molecular signals may transiently form droplets that help them interact with the right partners.

    “This is a very exciting turn in the field of cell biology,” Sharp says. “It is a whole new way of looking at biological systems that is richer and more meaningful.”

    Some of the MIT researchers, led by Young, have helped form a company called Dewpoint Therapeutics to develop potential treatments for a wide variety of diseases by exploiting cellular condensates.

    There is emerging evidence that cancer cells use condensates to control sets of genes that promote cancer, and condensates have also been linked to neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Huntington’s disease.

    The research was funded by the National Science Foundation, the National Institutes of Health, and the Koch Institute Support (core) Grant from the National Cancer Institute.

    Chemists build a better cancer-killing drill: Rice University designs molecular motors with an upgrade for activation with near-infrared light


    Houston, TX | Posted on May 29th, 2019

    Researchers at Rice University, Durham (U.K.) University and North Carolina State University reported their success at activating the motors with precise two-photon excitation via near-infrared light. Unlike the ultraviolet light they first used to drive the motors, the new technique does not damage adjacent, healthy cells.

    The team’s results appear in the American Chemical Society journal ACS Nano.

    The research led by chemists James Tour of Rice, Robert Pal of Durham and Gufeng Wang of North Carolina may be best applied to skin, oral and gastrointestinal cancer cells that can be reached for treatment with a laser. 

    In a 2017 Nature paper, the same team reported the development of molecular motors enhanced with small proteins that target specific cancer cells.

    Once in place and activated with light, the paddlelike motors spin up to 3 million times a second, allowing the molecules to drill through the cells’ protective membranes and killing them in minutes.

    Since then, researchers have worked on a way to eliminate the use of damaging ultraviolet light. In two-photon absorption, a phenomenon predicted in 1931 and confirmed 30 years later with the advent of lasers, the motors absorb photons in two frequencies and move to a higher energy state, triggering the paddles.

    A video produced in 2017 explains the basic concept of cell death via molecular motors. Video produced by Brandon Martin/Rice University.

    “Multiphoton activation is not only more biocompatible but also allows deeper tissue penetration and eliminates any unwanted side effects that may arise with the previously used UV light,” Pal said. 

    The researchers tested their updated motors on skin, breast, cervical and prostate cancer cells in the lab. Once the motors found their targets, lasers activated them with a precision of about 200 nanometers.

    In most cases, the cells were dead within three minutes, they reported. They believe the motors also drill through chromatin and other components of the diseased cells, which could help slow metastasis.

    Because the motors target specific cells, Tour said work is underway to adapt them to kill antibiotic-resistant bacteria as well.

    “We continue to perfect the molecular motors, aiming toward ones that will work with visible light and provide even higher efficacies of kill toward the cellular targets,” he said.

    Rice postdoctoral researcher Dongdong Liu is lead author of the paper. Co-authors are Rice alumni Victor Garcia-López, Lizanne Nilewski and Amir Aliyan, visiting research scientist Richard Gunasekera, and senior research scientist Lawrence Alemany and graduate student Tao Jin of North Carolina State.

    Wang is an assistant professor of chemistry at North Carolina State. Pal is an assistant professor of chemistry at Durham. Tour is the T.T. and W.F. Chao Chair in Chemistry as well as a professor of computer science and of materials science and nanoengineering at Rice.

    The Royal Society, the United Kingdom’s Engineering and Physical Sciences Research Council, the Discovery Institute, the Pensmore Foundation and North Carolina State supported the research.

    About Rice University
    Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,962 undergraduates and 3,027 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 2 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

    Follow Rice News and Media Relations via Twitter @RiceUNews.

    Copyright © Rice University

    University of Georgia – Microfluidic device may help researchers better understand (and isolate) Metastatic Cancer – “Finding the Needle in the Haystack”


    Needle Cancer U Georgia d2_JEHjN

    Instead of searching for a needle in a haystack, what if you were able to sweep the entire haystack to one side, leaving only the needle behind? That’s the strategy researchers in the University of Georgia College of Engineering followed in developing a new microfluidic device that separates elusive circulating tumor cells (CTCs) from a sample of whole blood.

    CTCs break away from cancerous tumors and flow through the bloodstream, potentially leading to new metastatic tumors. The isolation of CTCs from the blood provides a minimally invasive alternative for basic understanding, diagnosis and prognosis of metastatic cancer. But most studies are limited by technical challenges in capturing intact and viable CTCs with minimal contamination.
    “A typical sample of 7 to 10 milliliters of blood may contain only a few CTCs,” said Leidong Mao, a professor in UGA’s School of Electrical and Computer Engineering and the project’s principal investigator. “They’re hiding in whole blood with millions of white blood cells. It’s a challenge to get our hands on enough CTCs so scientists can study them and understand them.”
    Leidong Mao (right) and graduate student Yang Liu in lab
    Leidong Mao (right) and graduate student Yang Liu stand in Mao’s lab at UGA.
    Circulating tumor cells are also difficult to isolate because within a sample of a few hundred CTCs, the individual cells may present many characteristics. Some resemble skin cells while others resemble muscle cells. They can also vary greatly in size.
    “People often compare finding CTCs to finding a needle in a haystack,” said Mao. “But sometimes the needle isn’t even a needle.”
    To more quickly and efficiently isolate these rare cells for analysis, Mao and his team have created a new microfluidic chip that captures nearly every CTC in a sample of blood ­- more than 99% – a considerably higher percentage than most existing technologies.
    The team calls its novel approach to CTC detection “integrated ferrohydrodynamic cell separation,” or iFCS. They outline their findings in a study published in Lab on a Chip (“Tumor antigen-independent and cell size variation-inclusive enrichment of viable circulating tumor cells”).
    The new device could be “transformative” in the treatment of breast cancer, according to Melissa Davis, an assistant professor of cell and developmental biology at Weill Cornell Medicine and a collaborator on the project.
    “Physicians can only treat what they can detect,” Davis said. “We often can’t detect certain subtypes of CTCs, but with the iFCS device we will capture all the subtypes of CTCs and even determine which subtypes are the most informative concerning relapse and disease progression.”
    Davis believes the device may ultimately allow physicians to gauge a patient’s response to specific treatments much earlier than is currently possible.
    While most efforts to capture circulating tumor cells focus on identifying and isolating the few CTCs lurking in a blood sample, the iFCS takes a completely different approach by eliminating everything in the sample that’s not a circulating tumor cell.
    The device, about the size of a USB drive, works by funneling blood through channels smaller in diameter than a human hair. To prepare blood for analysis, the team adds micron-sized magnetic beads to the samples. The white blood cells in the sample attach themselves to these beads. As blood flows through the device, magnets on the top and bottom of the chip draw the white blood cells and their magnetic beads down a specific channel while the circulating tumor cells continue into another channel.
    The device combines three steps in one microfluidic chip, another advance over existing technologies that require separate devices for various steps in the process.
    “The first step is a filter that removes large debris in the blood,” said Yang Liu, a doctoral student in UGA’s department of chemistry and the paper’s co-lead author. “The second part depletes extra magnetic beads and the majority of the white blood cells. The third part is designed to focus remaining white blood cells to the middle of channel and to push CTCs to the side walls.”
    Wujun Zhao is the paper’s other lead author. Zhao, a postdoctoral scholar at Lawrence Berkeley National Laboratory, worked on the project while completing his doctorate in chemistry at UGA.
    “The success of our integrated device is that it has the capability to enrich almost all CTCs regardless of their size profile or antigen expression,” said Zhao. “Our findings have the potential to provide the cancer research community with key information that may be missed by current protein-based or size-based enrichment technologies.”
    The researchers say their next steps include automating the iFCS and making it more user-friendly for clinical settings. They also need to put the device through its paces in patient trials. Mao and his colleagues hope additional collaborators will join them and lend their expertise to the project.
    Source: University of Georgia

    MIT: How Tumors Behave on Acid: Acidic Environment Triggers Genes that Help Cancer Metastasize


    MIT-Tumor-Acidity_0

    In these tumor cells, acidic regions are labeled in red. Invasive regions of the cells, which express a protein called MMP14, are labeled in green. Image: Nazanin Rohani

    Acidic environment triggers genes that help cancer cells metastasize.

    Scientists have long known that tumors have many pockets of high acidity, usually found deep within the tumor where little oxygen is available. However, a new study from MIT researchers has found that tumor surfaces are also highly acidic, and that this acidity helps tumors to become more invasive and metastatic.

    The study found that the acidic environment helps tumor cells to produce proteins that make them more aggressive. The researchers also showed that they could reverse this process in mice by making the tumor environment less acidic.

    “Our findings reinforce the view that tumor acidification is an important driver of aggressive tumor phenotypes, and it indicates that methods that target this acidity could be of value therapeutically,” says Frank Gertler, an MIT professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study.

    Former MIT postdoc Nazanin Rohani is the lead author of the study, which appears in the journal Cancer Research.

    Mapping acidity

    Scientists usually attribute a tumor’s high acidity to the lack of oxygen, or hypoxia, that often occurs in tumors because they don’t have an adequate blood supply. However, until now, it has been difficult to precisely map tumor acidity and determine whether it overlaps with hypoxic regions.

    In this study, the MIT team used a probe called pH (Low) Insertion Peptide (pHLIP), originally developed by researchers at the University of Rhode Island, to map the acidic regions of breast tumors in mice. This peptide is floppy at normal pH but becomes more stable at low, acidic pH. When this happens, the peptide can insert itself into cell membranes. This allows the researchers to determine which cells have been exposed to acidic conditions, by identifying cells that have been tagged with the peptide.

    To their surprise, the researchers found that not only were cells in the oxygen-deprived interior of the tumor acidic, there were also acidic regions at the boundary of the tumor and the structural tissue that surrounds it, known as the stroma.

    “There was a great deal of tumor tissue that did not have any hallmarks of hypoxia that was quite clearly exposed to acidosis,” Gertler says. “We started looking at that, and we realized hypoxia probably wouldn’t explain the majority of regions of the tumor that were acidic.”

    illustration-of-tumor-spreading          A new study explores how an acidic environment drives tumor spread.

    Read More: How Does Tumor Acidity Help Cancer Spread

    Further investigation revealed that many of the cells at the tumor surface had shifted to a type of cell metabolism known as aerobic glycolysis. This process generates lactic acid as a byproduct, which could account for the high acidity, Gertler says. The researchers also discovered that in these acidic regions, cells had turned on gene expression programs associated with invasion and metastasis. Nearly 3,000 genes showed pH-dependent changes in activity, and close to 300 displayed changes in how the genes are assembled, or spliced.

    “Tumor acidosis gives rise to the expression of molecules involved in cell invasion and migration. This reprogramming, which is an intracellular response to a drop in extracellular pH, gives the cancer cells the ability to survive under low-pH conditions and proliferate,” Rohani says.

    Those activated genes include Mena, which codes for a protein that normally plays a key role in embryonic development. Gertler’s lab had previously discovered that in some tumors, Mena is spliced differently, producing an alternative form of the protein known as MenaINV (invasive). This protein helps cells to migrate into blood vessels and spread though the body.

    Another key protein that undergoes alternative splicing in acidic conditions is CD44, which also helps tumor cells to become more aggressive and break through the extracellular tissues that normally surround them. This study marks the first time that acidity has been shown to trigger alternative splicing for these two genes.

    Reducing acidity

    The researchers then decided to study how these genes would respond to decreasing the acidity of the tumor microenvironment. To do that, they added sodium bicarbonate to the mice’s drinking water. This treatment reduced tumor acidity and shifted gene expression closer to the normal state. In other studies, sodium bicarbonate has also been shown to reduce metastasis in mouse models.

    Sodium bicarbonate would not be a feasible cancer treatment because it is not well-tolerated by humans, but other approaches that lower acidity could be worth exploring, Gertler says. The expression of new alternative splicing genes in response to the acidic microenvironment of the tumor helps cells survive, so this phenomenon could be exploited to reverse those programs and perturb tumor growth and potentially metastasis.

    “Other methods that would more focally target acidification could be of great value,” he says.

    The research was funded by the Koch Institute Support (core) Grant from the National Cancer Institute, the Howard Hughes Medical Institute, the National Institutes of Health, the KI Quinquennial Cancer Research Fellowship, and MIT’s Undergraduate Research Opportunities Program.

    Other authors of the paper include Liangliang Hao, a former MIT postdoc; Maria Alexis and Konstantin Krismer, MIT graduate students; Brian Joughin, a lead research modeler at the Koch Institute; Mira Moufarrej, a recent graduate of MIT; Anthony Soltis, a recent MIT PhD recipient; Douglas Lauffenburger, head of MIT’s Department of Biological Engineering; Michael Yaffe, a David H. Koch Professor of Science; Christopher Burge, an MIT professor of biology; and Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science.

    Sprayable gel could help the body fight off cancer … after surgery


    sprayablegelA scanning electron microscope image of a gel developed by UCLA researchers that could help prevent cancer from recurring after surgery. Credit: University of California, Los Angeles

    Many people who are diagnosed with cancer will undergo some type of surgery to treat their disease—almost 95 percent of people with early-diagnosed breast cancer will require surgery and it’s often the first line of treatment for people with brain tumors, for example. But despite improvements in surgical techniques over the past decade, the cancer often comes back after the procedure.

    AAfter surgery sprayable gel kp69pm-800x533

    Now, a UCLA-led  has developed a spray gel embedded with immune-boosting drugs that could help. In a peer-reviewed study, the substance was successful half of the time in awakening lab animals’ immune systems to stop the cancer from recurring and inhibit it from spreading to other parts of the body.

    A paper describing the work is published online in the journal Nature Nanotechnology.

    The researchers, led by Zhen Gu, a professor of bioengineering at the UCLA Samueli School of Engineering and member of the UCLA Jonsson Comprehensive Cancer Center, tested the biodegradable spray gel in mice that had advanced melanoma tumors surgically removed. They found that the gel reduced the growth of the tumor cells that remained after surgery, which helped prevent recurrences of the cancer: After receiving the treatment, 50 percent of the mice survived for at least 60 days without their tumors regrowing.

    The spray not only inhibited the recurrence of tumors from the area on the body where it was removed, but it also controlled the development of tumors in other parts of the body, said Gu, who is also a member of the California NanoSystems Institute at UCLA.

    Cancer-treatment-655x353The substance will have to go through further testing and approvals before it could be used in humans. But Gu said that the scientists envision the gel being applied to the tumor resection site by surgeons immediately after the tumor is removed during surgery.

    “This sprayable gel shows promise against one of the greatest obstacles in curing cancer,” Gu said. “One of the trademarks of cancers is that it spreads. In fact, around 90 percent of people with cancerous tumors end up dying because of  recurrence or metastasis. Being able to develop something that helps lower this risk for this to occur and has low toxicity is especially gratifying.”

    The researchers loaded nanoparticles with an antibody specifically targeted to block CD47, a protein that cancer cells release as a “don’t-eat-me” signal. By blocking CD47, the antibody enables the immune system to find and ultimately destroy the cancer cells.

    The nanoparticles are made of calcium carbonate, a substance that is the main component of egg shells and is often found in rocks. Researchers chose  because it can be gradually dissolved in surgical wound sites, which are slightly acidic, and because it boosts the activity of a type of macrophage that helps rid the body of foreign objects, said Qian Chen, the study’s lead author and a  in Gu’s lab.

    “We also learned that the gel could activate T cells in the immune system to get them to work together as another line of attack against lingering  cells,” Chen said.

    Once the solution is sprayed on the surgical site, it quickly forms a gel embedded with the nanoparticles. The gel helps stop at the surgical site and promotes would healing; the nanoparticles gradually dissolve and release the anti-CD47 antibodies into the body.

    The  will continue testing the approach in animals to learn the optimal dose, best mix of nanoparticles and ideal treatment frequency, before testing the gel on human patients.

     Explore further: Gradual release of immunotherapy at site of tumor surgery prevents tumors from returning

    More information: Qian Chen et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment, Nature Nanotechnology (2018). DOI: 10.1038/s41565-018-0319-4

     

    Nanoscale blood test technique could lead to accelerated early diagnosis and personalized medicines


    A technique to get more information from the blood of cancer patients than previously possible has been developed.

    “We hope this technique could be a springboard for further research, from monitoring disease progression or recurrence, to identifying which treatment is best for each patient and potentially finding new biomarkers for early diagnosis.”- Professor Kostas Kostarelos

    The discovery could potentially accelerate early diagnosis, speed up drug discovery and lead to advancements in personalised medicines.

    The Cancer Research UK-funded study* is published in Advanced Materials today (Wednesday).

    The scientists, from the University of Manchester, collected blood samples from women with advanced ovarian cancer who were treated with a type of chemotherapy called CAELYX®.

    This chemotherapy drug is contained in a soft, lipid-based nanoparticle, called a liposome, which acts as a vessel to help minimise side effects**.

    Women gave a sample of blood, following an injection of CAELYX® over a course of 90 minutes as part of their treatment. By extracting the injected liposomes, the scientists were able to detect a wide variety of biomolecules that stuck to the surface of the liposome – called the ‘biomolecule corona’.

    Professor Kostas Kostarelos, lead author from the University of Manchester, said: “We’re astonished at how rich the information was on the surface of the liposomes taken from the blood. We hope this technique could be a springboard for further research, from monitoring disease progression or recurrence, to identifying which treatment is best for each patient and potentially finding new biomarkers for early diagnosis.”

    This is a step forward in developing a better technique to gather information from patients’ blood – a ‘halo effect’ of biomolecules sticking to the liposomes has been seen before, but only after dipping the nanoparticles in blood samples in a tube outside the patient’s body.

    Dr Marilena Hadjidemetriou, study author from the University of Manchester, said: “The blood is a potential goldmine of information, but there’s a challenge to amplify cancer signals that would otherwise be buried within the ‘noise’.

    “More abundant proteins mask rarer and smaller molecules that could be significant in helping us to understand disease progression or finding potential new drug targets. This technique overcomes this challenge.”

    Professor Caroline Dive, Cancer Research UK’s expert in liquid biopsies, said: “Finding a test to help diagnose, track and treat cancer is something many scientists are pursuing. Liquid biopsies are quicker, cheaper and less invasive than many other tests, and this technique is an important early step in developing such a test. Further work will reveal what the information captured using liposomes can tell us about the disease.”

    The researchers now hope to use this technique in mice to help find the best patterns of biomarkers to identify cancers in the early stages of disease as part of their Cancer Research UK Pioneer Award, which funds innovative ideas from any discipline that could revolutionise our understanding of cancer.

    Source

    How nanotechnology research could cure cancer – genetic diseases


    Genetic diseases may soon be a thing of the past thanks to nanotechnology, which employs tiny particles to manipulate cells and change our DNA.

    Here is how cancer treatment often runs today: a patient develops an aggressive tumor. A surgeon operates to remove the tumor, but a few cancer cells remain, hiding in the body. Chemotherapy is administered, weakening both patient and cancer cells. But the cancer does not die; it comes back and eventually kills the patient.

    Now imagine another scenario. After surgery, strands of DNA anchored in tiny gold particles are injected into the affected area. The DNA strands bind to the tumor cells, killing them directly, without the help of chemo. The healthy cells around the tumor cells, which don’t express the tumor gene, are untouched.

    Just like that, all the tumor cell stragglers are rendered harmless, corrected on the genetic level. The patient is cured, and without having to endure months of chemotherapy and its brutal side effects: hair loss, nausea and extreme weakness.

    The future of medicine won’t focus on treating the symptoms of a disease, according to reseachers: it will focus on curing it at the genetic level.

    Nanotechnology, the science of working with particles that are one billionth of a meter, is enabling scientists to change gene expression on the cellular level, potentially curing a host of diseases.

    “Nanotechnology medical developments over the coming years will have a wide variety of uses and could potentially save a great number of lives,” says Eleonore Pauwels, senior associate and scholar at the Wilson Center, an interdisciplinary policy research center.

    The science of using nanoparticles got its start with a lecture by theoretical physicist Richard Feynman in 1959, but because of the technical challenges, it is only in the past 10 years or so that the technology has really taken off for practical medical applications.

    Figuring out how to consistently create the right nanoparticle, get it into the right tissue, ensure it is not degraded and does what it was programmed to do, took some time.

    The science of nanotechnology depends on the fact that when things get super small, they function differently. Protein, for example, is a naturally occurring nanoparticle. A single protein molecule is a very different entity than a human being, which is made up of many protein molecules.

    Gold, which is used often in medicine, is red when broken down into tiny particles. That microscopic bright red color has been used for centuries to give red stained glass its color.

    “Because of their small size, engineered nanomaterials have unique properties that do not exist at the larger scale: increased surface area, charge, reactivity and other physicochemical properties, all of which may affect how nanomaterials interact with biological entities, like cells,” says Sara Brenner, assistant professor of nanobioscience at SUNY Polytechnic Institute.

    Scientists are learning to take advantage of those properties to create new treatments. One of the most powerful examples uses DNA, says Chad Mirkin, a professor at Northwestern University and director of the International Institute for Nanotechnology.

    DNA is rod shaped and normally would not be able to enter cells, which have developed protection against entry from foreign DNA segments.

    But by using nanotechnology, many little snippets of DNA can be attached to a tiny, round synthetic core. The receptors on cells that would block rod shaped DNA do not recognize the tiny spheres of DNA and allow it to enter.

    Using that property, a whole new class of treatments for genetic diseases is being developed.

    By being able to insert DNA into existing cells, scientists can “attack disease at its genetic root and turn off receptors that regulate how a cell functions, stopping a disease pathway in its tracks,” explains Mirkin.

    Right now, most of the research into developing therapies using spheres of DNA is focused on disease of the liver, says Mirkin, as anything a person takes in is going to be processed in the liver. Another area of research into nanotech treatments is the skin, as the treatment can be applied topically, making it easy to target one area.

    “Potential applications are virtually endless,” explains Brenner. “But some areas of investigation right now for gene therapy are cancer, diabetes, AIDS, cystic fibrosis and heart disease.”

    As research into using nanoparticles advances, scientists hope to be able to not just turn off specific signals in cells, but also eventually insert genes to correct for defects and cure more complex diseases.

    Called gene therapy, it would involve inserting larger fragments of DNA into cells that have faulty DNA. For example, cystic fibrosis is caused by a defective gene called CFTR. If scientists can figure out a way to get a non-defective copy of the gene into the cells and correct it, they could cure the disease.

    “Approximately 4,000 diseases have been found to have a genetic component and are therefore potential targets for gene therapy,” according to Brenner.

    While nanotechnology has the potential to revolutionize medicine and how we view treatment of diseases, there are still kinks to work out.

    Some of the challenges with nanotechnology include how to get nanoparticles into the right cells and tissues, and how to get them into the cells safely without the nanoparticles degrading.

    Nanotechnology is still in its infancy, however. It’s only recently that we were able to produce microscopes that allowed us to see and manipulate nanoparticles. 

    Research requires bringing together a number of disciplines like chemistry, biomedical engineering, biology and physics. But pharmaceutical companies have already begun work on creating treatments using nanotech, and many are in various stages of development now. “It’s not a pipe dream,” says Mirkin. Being able to cure genetic diseases of all kinds is on the horizon.

    MD Anderson Cancer Center: U of Texas (Houston) scientist wins Nobel Prize for breakthrough cancer treatment


    Allison’s groundbreaking work with T cells helped him net the award. Photo courtesy of MD Anderson Cancer Center

    The already much-heralded University of Texas MD Anderson Cancer Center has just scored global bragging rights. Jim Allison, Ph.D., a scientist at MD Anderson Cancer Center, has been awarded the 2018 Nobel Prize in Physiology or Medicine, it was announced on October 1, 2018.

    Allison, who is the chair of Immunology and executive director of the Immunotherapy Platform, is the first MD Anderson scientist to receive the world’s most coveted award for discoveries in the fields of life sciences and medicine. Allison won for his work in launching an effective new way to attack cancer by treating the immune system rather than the tumor, according to a release.

    “I’m honored and humbled to receive this prestigious recognition,” Allison says in a statement. “A driving motivation for scientists is simply to push the frontiers of knowledge. I didn’t set out to study cancer, but to understand the biology of T cells, these incredible cells to travel our bodies and work to protect us.”

    Allison shares the award with Tasuku Honjo, M.D., Ph.D., of Kyoto University in Japan. When announcing the honor, the Nobel Assembly of Karolinska Institute in Stockholm noted in a statement that “stimulating the ability of our immune system to attack tumor cells, this year’s Nobel Prize laureates have established an entirely new principle for cancer therapy.”

    The prize recognizes Allison’s basic science discoveries on the biology of T cells, the adaptive immune system’s soldiers, and his invention of immune checkpoint blockade to treat cancer. According to MD Anderson, Allison’s crucial insight was to block a protein on T cells that acts as a brake on their activation, freeing the T cells to attack cancer. He developed an antibody to block the checkpoint protein CTLA-4 and demonstrated the success of the approach in experimental models.

    Allison’s work led to development of the first immune checkpoint inhibitor drug which would become the first to extend the survival of patients with late-stage melanoma. Follow-up studies show 20 percent of those treated live for at least three years with many living for 10 years and beyond, unprecedented results, according to the cancer center.

    “Jim Allison’s accomplishments on behalf of patients cannot be overstated,” says MD Anderson president Peter WT Pisters, M.D., in a statement. “His research has led to life-saving treatments for people who otherwise would have little hope. The significance of immunotherapy as a form of cancer treatment will be felt for generations to come.”

    “I never dreamed my research would take the direction it has,” Allison adds. “It’s a great, emotional privilege to meet cancer patients who’ve been successfully treated with immune checkpoint blockade. They are living proof of the power of basic science, of following our urge to learn and to understand how things work.”