New Cancer Research – Converting Cancer Cells to Fat Cells to Stop Cancer’s Spread


A method for fooling breast cancer cells into fat cells has been discovered by researchers from the University of Basel.

The team were able to transform EMT-derived breast cancer cells into fat cells in a mouse model of the disease – preventing the formation of metastases. The proof-of-concept study was published in the journal Cancer Cell. 

Malignant cells can rapidly respond and adapt to changing microenvironmental conditions, by reactivating a cellular process called epithelial-mesenchymal transition (EMT), enabling them to alter their molecular properties and transdifferentiate into a different type of cell (cellular plasticity).

Senior author of the study Gerhard Christofori, professor of biochemistry at the University of Basel, commented in a recent press release: “The breast cancer cells that underwent an EMT not only differentiated into fat cells, but also completely stopped proliferating.”

“As far as we can tell from long-term culture experiments, the cancer cells-turned-fat cells remain fat cells and do not revert back to breast cancer cells,” he explained.

Epithelial-mesenchymal transition and cancer 

Cancer cells can exploit EMT – a process that is usually associated with the development of organs during embryogenesis – in order to migrate away from the primary tumor and form secondary metastases. Cellular plasticity is linked to cancer survival, invasion, tumor heterogeneity and resistance to both chemo and targeted therapies. In addition, EMT and the inverse process termed mesenchymal-epithelial transition (MET) both play a role in a cancer cell’s ability to metastasize.

Using mouse models of both murine and human breast cancer the team investigated whether they could therapeutically target cancer cells during the process of EMT – whilst the cells are in a highly plastic state. When the mice were administered Rosiglitazone in combination with MEK inhibitors it provoked the transformation of the cancer cells into post-mitotic and functional adipocytes (fat cells). In addition, primary tumor growth was suppressed and metastasis was prevented. 

Cancer cells marked in green and a fat cell marked in red on the surface of a tumor (left). After treatment (right), three former cancer cells have been converted into fat cells. The combined marking in green and red causes them to appear dark yellow. Credit: University of Basel, Department of Biomedicine

Christofori highlights the two major findings in the study: 

“Firstly, we demonstrate that breast cancer cells that undergo an EMT and thus become malignant, metastatic and therapy-resistant, exhibit a high degree of stemness, also referred to as plasticity. It is thus possible to convert these malignant cells into other cell types, as shown here by a conversion to adipocytes.”

“Secondly, the conversion of malignant breast cancer cells into adipocytes not only changes their differentiation status but also represses their invasive properties and thus metastasis formation and their proliferation. Note that adipocytes do not proliferate anymore, they are called ‘post-mitotic’, hence the therapeutic effect.”

Since both drugs used in the preclinical study were FDA-approved the team are hopeful that it may be possible to translate this therapeutic approach to the clinic. 

“Since in patients this approach could only be tested in combination with conventional chemotherapy, the next steps will be to assess in mouse models of breast cancer whether and how this trans-differentiation therapy approach synergizes with conventional chemotherapy. In addition, we will test whether the approach is also applicable to other cancer types. These studies will be continued in our laboratories in the near future.”

Journal Reference: Ronen et al. Gain Fat–Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis. Cancer Cell. (2019). Available at: https://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30573-7 

Gerhard Christofori was speaking to Laura Elizabeth Lansdowne, Science Writer for Technology Networks

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Washington State U – Bio-inspired nanoscale Research – Nano-Flowers may lead lead to more effective drug delivery and diagnostics for cancer and other illnesses


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Schematic representation of the movement of the flower-like particle as it makes its way through a cellular trap to deliver therapeutic genes.
Credit: WSU

Washington State University researchers have developed a novel way to deliver drugs and therapies into cells at the nanoscale without causing toxic effects that have stymied other such efforts.

The work could someday lead to more effective therapies and diagnostics for cancer and other illnesses.

Led by Yuehe Lin, professor in WSU’s School of Mechanical and Materials Engineering, and Chunlong Chen, senior scientist at the Department of Energy’s Pacific Northwest National Laboratory (PNNL), the research team developed biologically inspired materials at the nanoscale that were able to effectively deliver model therapeutic genes into tumor cells. They published their results in the journal, Small.

Researchers have been working to develop nanomaterials that can effectively carry therapeutic genes directly into the cells for the treatment of diseases such as cancer. The key issues for gene delivery using nanomaterials are their low delivery efficiency of medicine and potential toxicity.

“To develop nanotechnology for medical purposes, the first thing to consider is toxicity — That is the first concern for doctors,” said Lin.

The flower-like particle the WSU and PNNL team developed is about 150 nanometers in size, or about one thousand times smaller than the width of a piece of paper. It is made of sheets of peptoids, which are similar to natural peptides that make up proteins. The peptoids make for a good drug delivery particle because they’re fairly easy to synthesize and, because they’re similar to natural biological materials, work well in biological systems.

The researchers added fluorescent probes in their peptoid nanoflowers, so they could trace them as they made their way through cells, and they added the element fluorine, which helped the nanoflowers more easily escape from tricky cellular traps that often impede drug delivery.

The flower-like particles loaded with therapeutic genes were able to make their way smoothly out of the predicted cellular trap, enter the heart of the cell, and release their drug there.

“The nanoflowers successfully and rapidly escaped (the cell trap) and exhibited minimal cytotoxicity,” said Lin.

After their initial testing with model drug molecules, the researchers hope to conduct further studies using real medicines.

“This paves a new way for us to develop nanocargoes that can efficiently deliver drug molecules into the cell and offers new opportunities for targeted gene therapies,” he said.

The WSU and PNNL team have filed a patent application for the new technology, and they are seeking industrial partners for further development.

Story Source:

Materials provided by Washington State UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Yang Song, Mingming Wang, Suiqiong Li, Haibao Jin, Xiaoli Cai, Dan Du, He Li, Chun-Long Chen, Yuehe Lin. Efficient Cytosolic Delivery Using Crystalline Nanoflowers Assembled from Fluorinated PeptoidsSmall, 2018; 14 (52): 1803544 DOI: 10.1002/smll.201803544

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

 

MIT – Measuring cancer cell “fitness” reveals drug susceptibility and the potential to treat non-responsive cancer cells


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MIT engineers have designed a system that can repeatedly measure cancer cells as they flow through an array of mass sensors. Once the cells reach the end, they are collected for RNA-sequencing. Image courtesy of the researchers.

Courtesy of MIT News

Together, cell growth rate and gene expression shed light on why some tumor cells survive treatment.

 

By studying both the physical and genomic features of cancer cells, MIT researchers have come up with a new way to investigate why some cancer cells survive drug treatment while others succumb.

Their new approach, which combines measurements of cell mass and growth rate with analysis of a cell’s gene expression, could be used to reveal new drug targets that would make cancer treatment more effective. Exploiting these targets could help knock out the defenses that cells use to overcome the original drug treatment, the researchers say.

In a paper appearing in the Nov. 28 issue of the journal Genome Biology, the researchers identified a growth signaling pathway that is active in glioblastoma cells that are resistant to an experimental type of drug known as an MDM2 inhibitor.

“By measuring a cell’s mass and growth rate immediately prior to single-cell RNA-sequencing, we can now use a cell’s ‘fitness’ to classify it as responsive or nonresponsive to a drug, and to relate this to underlying molecular pathways,” says Alex K. Shalek, the Pfizer-Laubach Career Development Assistant Professor of Chemistry, a member of MIT’s Institute for Medical Engineering and Science (IMES), an extramural member of the Koch Institute for Integrative Cancer Research, and an associate member of the Ragon and Broad Institutes.

Shalek and Scott Manalis, the Andrew and Erna Viterbi Professor in the MIT departments of Biological Engineering and Mechanical Engineering and a member of the Koch Institute, are the senior authors of the study. The paper’s lead author is Robert Kimmerling, a recent MIT PhD recipient.

Cancer cell analysis

About a decade ago, Manalis’ lab invented a technology that allows researchers to measure the mass of single cells. In recent years, they have adapted the device, which measures cells’ masses as they flow through tiny channels, so that it can also measure cell growth rates by repeatedly weighing the cells over short periods of time.

Last year, working with researchers at Dana-Farber Cancer Institute (DFCI), Manalis and his colleagues used this approach to test drug responses of tumor cells from patients with multiple myeloma, a type of blood cancer. After treating the cells with three different drugs, the researchers measured the cells’ growth rates and found they were correlated with the cells’ susceptibility to the treatment.

“Single-cell biophysical properties such as mass and growth rate provide early indicators of drug response, thereby offering the potential to delineate sensitive cells from resistant cells while they are still viable,” Manalis says.

In their new study, the researchers wanted to add a genomic component, which they hoped could help reveal why only certain cells are susceptible to a particular drug. “We wanted to be able to take those measurements and add on some of the biological context for why a cell is growing a certain way or behaving a certain way,” Kimmerling says.

To accomplish this, Kimmerling and Manalis teamed up with Shalek, who has extensive experience in sequencing the messenger RNA (mRNA) of individual cells. This information can provide a snapshot of which genes are being expressed in a single cell at a particular moment.

The researchers modified the cell-weighing system so that cells would be spaced evenly as they flowed through, making it easier to collect them one at a time when they exit the system. The cells are weighed several times over the course of 20 minutes to determine growth rate, and as soon as they reach the end of the channel, they are immediately captured and ruptured to release their RNA for analysis. Shalek’s lab then sequenced the RNA of each of the cells. This approach enabled the mass and growth rate of each cell to be directly linked to its gene expression.

Once they had the system working, the researchers collaborated with Keith Ligon and his lab at DFCI to analyze cancer cells derived from a patient with glioblastoma, an aggressive type of brain cancer. The researchers treated the cells with an MDM2 inhibitor, a type of drug that helps to boost the function of p53, a protein that helps cells stop tumor formation. Such drugs are now in clinical trials to treat glioblastoma. In animal studies, this drug has been effective against tumors, but the tumors often grow back later.

In this study, the researchers hoped to find out why some glioblastoma cells survive MDM2 treatment. They treated the cells, measured their growth rates about 16 hours after the treatment, and then sequenced their RNA. “Before the cells have lost viability, we can measure their mass and their growth rate to reveal drug response heterogeneity to that treatment, and then link that with their gene expression,” Kimmerling says.

Importantly, the researchers found subpopulations of cells that were not responsive to the drug. RNA sequencing revealed that in cells that were responsive, genes required for programmed cell death were turned on. Meanwhile, in cells that did not seem to be vulnerable to the drug, genes involved in mTOR, a signaling pathway involved in growth and survival, were turned up.

“What we’re excited about here is we now have this list of biological targets to look into,” Kimmerling says. “We can start to generate testable hypotheses from these gene expression signatures that are more highly expressed in the cells that continue to grow after drug treatment.”

Possible drug targets

The researchers now plan to explore the possibility of targeting some of the genes that were turned up on the non-responding cells, in hopes of developing drugs that could be used together with the original MDM2 inhibitor. They also hope to adapt this approach for other types of cancers. Some, such as blood cancers, are easier to study than solid tumors, which are more difficult to separate into single cells.

“The hope is that we’ll be able to apply this technology to any sample that can be dissociated into a single-cell population,” Kimmerling says.

Another possible application of the cell-growth measurement technology is studying tumor cells from individual patients to try to predict how they will respond to a particular drug. Kimmerling, Manalis, and others have founded a company called Travera, which has licensed the technology and hopes to develop it for patient use. The company is currently not working on the RNA sequencing aspect of the technology, but that element could also be valuable to incorporate in the future, Kimmerling says.

The research was funded by the Cancer Systems Biology Consortium U54 Research Center and the Cancer Center Support (core) Grant from the National Cancer Institute; the Searle Scholars Program; the Beckman Young Investigator Program; the National Institutes of Health, including an NIH New Innovator Award; the Pew-Stewart Scholars; and a Sloan Fellowship in Chemistry.

Researchers Develop a universal DNA Nano-signature for early cancer detection – University of Queensland


Killer T cells surround cancer cell. Credit: NIH

Researchers from the University of Queensland’s Australian Institute for Bioengineering and Nanotechnology (AIBN) have discovered a unique nano-scaled DNA signature that appears to be common to all cancers.

Based on this discovery, the team has developed a  that enables  to be quickly and easily detected from any tissue type, e.g. blood or biopsy.

The study, which was supported by a grant from the National Breast Cancer Foundation and is published in the journal Nature Communications, reveals new insight about how epigenetic reprogramming in cancer regulates the physical and chemical properties of DNA and could lead to an entirely new approach to point-of-care diagnostics.

“Because cancer is an extremely complicated and variable disease, it has been difficult to find a simple signature common to all cancers, yet distinct from healthy ,” explains AIBN researcher Dr. Abu Sina.

To address this, Dr. Sina and Dr. Laura Carrascosa, who are working with Professor Matt Trau at AIBN, focussed on something called circulating free DNA.

Like healthy cells,  are always in the process of dying and renewing. When they die, they essentially explode and release their cargo, including DNA, which then circulates.

“There’s been a big hunt to find whether there is some distinct DNA signature that is just in the cancer and not in the rest of the body,” says Dr. Carrascosa.

So they examined epigenetic patterns on the genomes of cancer cells and healthy cells. In other words, they looked for patterns of molecules, called methyl groups, which decorate the DNA. These methyl groups are important to cell function because they serve as signals that control which genes are turned on and off at any given time.

In healthy cells, these methyl groups are spread out across the genome. However, the AIBN team discovered that the genome of a cancer cell is essentially barren except for intense clusters of methyl groups at very specific locations.

This unique signature—which they dubbed the cancer “methylscape”, for methylation landscape—appeared in every type of breast cancer they examined and appeared in other forms of cancer, too, including prostate cancer, colorectal cancer and lymphoma.

“Virtually every piece of cancerous DNA we examined had this highly predictable pattern,” says Professor Trau.

He says that if you think of a cell as a hard-drive, then the new findings suggest that cancer needs certain genetic programmes or apps in order to run.

“It seems to be a general feature for all cancer,” he says. “It’s a startling discovery.”

They also discovered that, when placed in solution, those intense clusters of  cause cancer DNA fragments to fold up into three-dimensional nanostructures that really like to stick to gold.

Taking advantage of this, the researchers designed an assay which uses gold nanoparticles that instantly change colour depending on whether or not these 3-D nanostructures of cancer DNA are present.

“This happens in one drop of fluid,” says Trau. “You can detect it by eye, it’s as simple as that.”

The technology has also been adapted for electrochemical systems, which allows inexpensive and portable detection that could eventually be performed using a mobile phone.

So far they’ve tested the new technology on 200 samples across different types of human cancers, and . In some cases, the accuracy of cancer detection runs as high as 90%.

“It works for tissue derived genomic DNA and blood derived circulating free DNA,” says Sina. “This new discovery could be a game-changer in the field of point of care cancer diagnostics.” It’s not perfect yet, but it’s a promising start and will only get better with time, says the team.

“We certainly don’t know yet whether it’s the Holy Grail or not for all cancer diagnostics,” says Trau, “but it looks really interesting as an incredibly simple universal marker of cancer, and as a very accessible and inexpensive technology that does not require complicated lab based equipment like DNA sequencing.”

More information: Abu Ali Ibn Sina et al, Epigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker, Nature Communications(2018).  DOI: 10.1038/s41467-018-07214-w

Provided by University of Queensland

Explore further: New cancer monitoring technology worth its weight in gold

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.

University of Cambridge: Researchers to target hard-to-treat cancers


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A £10 million interdisciplinary collaboration is to target the most challenging of cancers using nanomedicine.

“We are going to pierce through the body’s natural barriers and deliver anti-cancer drugs to the heart of the tumour.” – George Malliaras

While the survival rate for most cancers has doubled over the past 40 years, some cancers such as those of the pancreas, brain, lung and oesophagus still have low survival rates.

Such cancers are now the target of an Interdisciplinary Research Collaboration (IRC) led by the University of Cambridge and involving researchers from Imperial College London, University College London and the Universities of Glasgow and Birmingham.

“Some cancers are difficult to remove by surgery and highly invasive, and they are also hard to treat because drugs often cannot reach them at high enough concentration,” explains George Malliaras, Prince Philip Professor of Technology in Cambridge’s Department of Engineering, who leads the IRC. “Pancreatic tumour cells, for instance, are protected by dense stromal tissue, and tumours of the central nervous system by the blood-brain barrier.”

The aim of the project, which is funded for six years by the Engineering and Physical Sciences Research Council, is to develop an array of new delivery technologies that can deliver almost any drug to any tumour in a large enough concentration to kill the cancerous cells.

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Chemists, engineers, material scientists and pharmacologists will focus on developing particles, injectable gels and implantable devices to deliver the drugs. Cancer scientists and clinicians from the Cancer Research UK Cambridge Centre and partner sites will devise and carry out clinical trials. Experts in innovative manufacturing technologies will ensure the devices are able to be manufactured and robust enough to withstand surgical manipulation.

One technology the team will examine is the ability of advanced materials to self-assemble and entrap drugs inside metal-organic frameworks. These structures can carry enormous amounts of drugs, and be tuned both to target the tumour and to release the drug at an optimal rate.

“We are going to pierce through the body’s natural barriers,” says Malliaras, “and deliver anti-cancer drugs to the heart of the tumour.”

Dr Su Metcalfe, a member of George Malliaras’s team and who is already using NanoBioMed to treat Multuple Sclerosis, added “the power of nanotechnology to synergise with potent anti-cancer drugs will be profound and the award will speed delivery to patients.”

Nanoplatform developed with three (3) molecular imaging modalities for tumor diagnosis – Making it possible to expand detection to more types of cancer


nanoplatform for tumor diagnosisThe composition and application of the JANUS nanoplatform for multimodal medical imaging. Credit: Marco Filice

Researchers at the Complutense University of Madrid (UCM) have developed a hybrid nanoplatform that locates tumours using three different types of contrast simultaneously to facilitate multimodal molecular medical imaging: magnetic resonance imaging (MRI), computed tomography (CT) and fluorescence optical imaging (OI).

The results of this study, led by the UCM Life Sciences Nanobiotechnology research team directed by Marco Filice and published in ACS Applied Materials & Interfaces, represent a major advance in medical diagnosis since just one session using a single contrast medium yields more precise, specific results with higher resolution, sensitivity and capacity to penetrate tissues.

“No single molecular imaging modality provides a perfect diagnosis. Our nanoplatform is designed to enable multimodal molecular imaging, thus overcoming the intrinsic limitations of each single image modality while maximising their advantages,” noted Marco Filice, a researcher in the Department of Chemistry and Pharmaceutical Sciences at the Complutense University of Madrid and the director of the study.

The platform, which has been tested on mice, targets solid cancers such as sarcomas. “However, due to its flexibility, the proposed nanoplatform can be modified, and with a suitable design of recognition element siting, it will be possible to expand detection to more types of cancer,” Filice said.

Named after the Roman god Janus, usually depicted as having two faces, these nanoparticles also “have two opposing faces, one of iron oxide embedded in a silica matrix that serves as a contrast medium for MRI and another of gold for CT,” explained Alfredo Sánchez, a researcher in the UCM Department of Analytical Chemistry and the first author of the study.

In addition, a molecular probe sited in a specific manner in the golden area permits fluorescence optical imaging while a peptide selective for hyperexpressed receptors in tumours (RGD sequence) and sited on the silica surface enveloping the  identifies the tumour and makes it possible to direct and transport the nanoplatform to its target.

Once the research team had synthesised the nanoparticles and determined their characteristics and toxicity, they then tested them in mouse models reared to present a fibrosarcoma in the right leg. The nanoparticle was injected in the tail. “Excellent imaging results were obtained for each modality tested,” reported Filice.

Although there is still much to do before these experiments can be applied to humans, this research shows that personalised treatment is closer than ever to becoming a reality, thanks to nanotechnology and biotechnology.

 Explore further: Nanoparticles on track to distinguish tumour tissue

More information: Alfredo Sánchez et al, Hybrid Decorated Core@Shell Janus Nanoparticles as a Flexible Platform for Targeted Multimodal Molecular Bioimaging of Cancer, ACS Applied Materials & Interfaces (2018). DOI: 10.1021/acsami.8b10452

 

New micro-platform reveals cancer cells’ natural behavior


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Fluorescence images of pancreatic cancer micro-tumors after overnight culturing. Papillary structures pile up on micro-attachment sites (diameter 30?m), with numerous cells visible per patch. The rightmost micro-tumor has extended over two attachment sites. Nuclei, actin filaments, and microtubules are labeled with blue, green and red fluorescent markers respectively. Credit: Miyatake Y. et al., Scientific Reports, Sept. 19, 2018

A new cell culture platform allows researchers to observe never-before-seen behaviors of live cancer cells under the microscope, leading to explanations of long-known cancer characteristics.

The easy-to-produce platform developed by Hokkaido University researchers offers cancer cells micro-scale attachment sites that elicit never-before-seen behaviors highly relevant to cancer’s clinical properties. The observation of these behaviors shed light on the mechanisms behind well-known properties of pancreatic cancer, one of the most lethal malignant tumors, and may lead to the identification of new treatment targets.

“Cancer studies so far either use cell cultures in which cancer cells don’t necessarily behave naturally, or tissue samples that don’t allow live observation. So there is a big gap in our knowledge of how cancer cells actually behave,” says Assistant Professor Yukiko Miyatake, who led the study and focuses on cancer development mechanisms. To close this gap, she teamed up with Associate Professor Kaori Kuribayashi-Shigetomi who specializes on micro-nano-scale bio-engineering.

Together they created a new cell culture substrate from a coated glass slide with etched islands of 30?m diameter. For healthy cells, this is just enough space for one or two to attach. But when the researchers seeded them with pancreatic cancer cells (although they also tried other cancer cells with similar results) and incubated them overnight, the cells self-organized into micro-tumors that could move in a concerted way, as if it were one organism. Precursors to this turned out to be papillary structures that accommodate 4 or more cells by cell-in-cell invasion. This process, called entosis, is so far known only as a step in cell degradation. Here, the incorporated cells remained alive and, to their surprise, the incorporation was reversible.

When they treated the micro-tumors with the widely used anti-cancer agent Nocodazole, the micro-tumor disintegrated, but the now-detached cells survived. Moreover, the researchers observed the micro-tumors “fishing” for surrounding dead cells and ingesting them, in the process releasing chemical markers typical for dead cells. These markers ended up on the cancer cells’ surfaces, presumably masking them and enabling them to evade the immune system’s killer cells.

Striving to reduce the suffering cancer causes, Miyatake says: “I hope this easy and low-cost technique will find widespread adoption. If the discoveries made during these first observations are physiologically or pathologically relevant phenomena, many more new hints may be gleaned for the development of more effective cancer treatment approaches.”

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Materials provided by Hokkaido UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Yukiko Miyatake, Kaori Kuribayashi-Shigetomi, Yusuke Ohta, Shunji Ikeshita, Agus Subagyo, Kazuhisa Sueoka, Akira Kakugo, Maho Amano, Toshiyuki Takahashi, Takaharu Okajima, Masanori Kasahara. Visualising the dynamics of live pancreatic microtumours self-organised through cell-in-cell invasionScientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-32122-w

 

Hokkaido University. “New micro-platform reveals cancer cells’ natural behavior.” ScienceDaily. ScienceDaily, 19 September 2018. <www.sciencedaily.com/releases/2018/09/180919100952.htm>.