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.”

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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.”

Story Source:

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>.

Discovery: How groups of cells are able to build our tissues and organs while we are still embryos – Understanding ‘how’ may help us treat Cancer more effectively


 

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Ever wondered how groups of cells managed to build your tissues and organs while you were just an embryo?

Using state-of-the-art techniques he developed, UC Santa Barbara researcher Otger Campàs and his group have cracked this longstanding mystery, revealing the astonishing inner-workings of how embryos are physically constructed.

Not only does it bring a century-old hypothesis into the modern age, the study and its techniques provide the researchers a foundation to study other questions key to human health, such as how cancers form and spread or how to engineer organs.

“In a nutshell, we discovered a fundamental physical mechanism that cells use to mold embryonic tissues into their functional 3D shapes,” said Campàs, a professor of mechanical engineering in UCSB’s College of Engineering who holds the Duncan & Suzanne Mellichamp Chair in Systems Biology. His group investigates how living systems self organize to build the remarkable structures and shapes found in nature.

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Cells coordinate by exchanging biochemical signals, but they also hold to and push on each other to build the body structures we need to live, such as the eyes, lungs and heart. And, as it turns out, sculpting the embryo is not far from glass molding or 3D printing. In their new work,”A fluid-to-solid jamming transition underlies vertebrate body axis elongation,” published in the journal Nature, Campàs and colleagues reveal that cell collectives switch from fluid to solid states in a controlled manner to build the vertebrate embryo, in a way similar to how we mold glass into vases or 3D print our favorite items. Or, if you like, we 3D print ourselves, from the inside.

Most objects begin as fluids. From metallic structures to gelatin desserts, their shape is made by pouring the molten original materials into molds, then cooling them to get the solid objects we use.

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A fluid-to-solid jamming transition underlies vertebrate body axis elongation

As in a Chihuly glass sculpture, made by carefully melting portions of glass to slowly reshape it into life, cells in certain regions of the embryo are more active and ‘melt’ the tissue into a fluid state that can be restructured. Once done, cells ‘cool down’ to settle the tissue shape, Campàs explained.

“The transition from fluid to solid tissue states that we observed is known in physics as ‘jamming’,” Campàs said. “Jamming transitions are a very general phenomena that happens when particles in disordered systems, such as foams, emulsions or glasses, are forced together or cooled down.”

This discovery was enabled by techniques previously developed by Campàs and his group to measure the forces between cells inside embryos, and also to exert miniscule forces on the cells as they build tissues and organs. Using zebrafish embryos, favored for their optical transparency but developing much like their human counterparts, the researchers placed tiny droplets of a specially engineered ferromagnetic fluid between the cells of the growing tissue.

The spherical droplets deform as the cells around them push and pull, allowing researchers to see the forces that cells apply on each other. And, by making these droplets magnetic, they also could exert tiny stresses on surrounding cells to see how the tissue would respond.

“We were able to measure physical quantities that couldn’t be measured before, due to the challenge of inserting miniaturized probes in tiny developing embryos,” said postdoctoral fellow Alessandro Mongera, who is the lead author of the paper.

“Zebrafish, like other vertebrates, start off from a largely shapeless bunch of cells and need to transform the body into an elongated shape, with the head at one end and tail at the other,” Campàs said.

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The physical reorganization of the cells behind this process had always been something of a mystery. Surprisingly, researchers found that the cell collectives making the tissue were physically like a foam (yes, as in beer froth) that jammed during development to ‘freeze’ the tissue architecture and set its shape.

These observations confirm a remarkable intuition made by Victorian-era Scottish mathematician D’Arcy Thompson 100 years ago in his seminal work “On Growth and Form.”

Darcy Thompson Ms48534_13Read About: D’Arcy Wentworth Thompson

“He was convinced that some of the physical mechanisms that give shapes to inert materials were also at play to shape living organisms. Remarkably, he compared groups of cells to foams and even the shaping of cells and tissues to glassblowing,” Campàs said. A century ago, there were no instruments that could directly test the ideas Thompson proposed, Campàs added, though Thompson’s work continues to be cited to this day.

The new Nature paper also provides a jumping-off point from which the Campàs Group researchers can begin to address other processes of embryonic development and related fields, such as how tumors physically invade surrounding tissues and how to engineer organs with specific 3D shapes.

“One of the hallmarks of cancer is the transition between two different tissue architectures. This transition can in principle be explained as an anomalous switch from a solid-like to a fluid-like tissue state,” Mongera explained. “The present study can help elucidate the mechanisms underlying this switch and highlight some of the potential druggable targets to hinder it.”

Alessandro Mongera, Payam Rowghanian, Hannah J. Gustafson, Elijah Shelton, David A. Kealhofer, Emmet K. Carn, Friedhelm Serwane, Adam A. Lucio, James Giammona & Otger Campàs

Nature (2018)

DOI: 10.1038%2Fs41586-018-0479-2

Exploring Nanotechnology to Enhance Treatment, Diagnosis & Drug Discovery


What can you do with a liberal arts degree? Native New Yorker Daniel Heller, PhD, majored in history, added in some basic science courses, and started his working life as a middle school science teacher. After taking some additional chemistry coursework during non-teaching hours, Heller parlayed it all into a doctorate in chemistry from the University of Illinois.

Today he is a biomedical engineer at Memorial Sloan Kettering Cancer Center (MSKCC), New York City, where his Cancer Nanomedicine Laboratory team invents new technologies that can assist health care in helping human kind.

Heller chuckled when mentioning his circuitous life path and some of the stops along the way: performing as a wizard at a Renaissance Fair (“…liquid nitrogen turns into a pretty impressive potion…”), trying to master the Argentine tango, appreciating his brother’s equally non-traditional path as a drummer in heavy metal bands, and happily settling into married life with his wife who is a primary care physician.

In recent years, he has also managed to garner solid industry credentials in the form of awards, including the NSF CAREER Award (2018), Pershing Square Sohn Prize for Young Innovators in Cancer Research (2017), and NIH Director’s New Innovator Award (2012), among others.

“I like inventing,” Heller stated simply. “In my lab, we often think of ourselves as biomedical engineers whose primary goal is invent new technologies to improve cancer research, diagnosis, and therapy.

Only when I arrived at MSKCC did I realize how far that is from the way biologists think. I was trained that our goal is to invent, and to learn new science along the way, while a biologist’s goal is to understand nature and develop tools mainly as a means to an end. I didn’t have a huge biomedical background coming in, but by talking to the people around me at Sloan Kettering and Weill Cornell Medicine [where he is an Assistant Professor], I have learned a great deal.”

As detailed on his laboratory website (www.mskcc.org/research-areas/labs/daniel-heller), Heller and team are “… developing nanomedicines to target precision agents to disease sites, including to metastatic cancers. We are also addressing the problem of the early detection of cancer and other diseases by building implantable nanosensors.

To enable the discovery of new medicines, we also are inventing new nanosensors and imaging tools to accelerate drug development and biomedical research.”

Back to Top | Article Outline

Nanoparticles in Treatment

Heller told Oncology Times that it all begins with interaction and collaboration. “We are lucky because we get to dig deep with the clinicians, clinician/scientists, and biologists to understand exactly what might be wrong with a particular mode of therapy,” said Heller of his development process. “An oncologist might talk to us about a drug or class of therapies that have particular problems and specific side effects, such as dose-limiting toxicity that prevents people from getting enough of a therapy to adequately inhibit the target in the tumor.”

He added that problems often stem from the fact that a drug negatively affects tissue that is not part of the tumor. “Can we avoid that one vulnerable tissue that will really mess up the use of this drug for treating the tumor? Can we prevent the drug from getting into that tissue?” asked Heller rhetorically. Clearly, he believes it is possible with the help of nanoparticles.

He noted that people erroneously think of nanoparticles as being “the smallest of the small.” But small molecule drugs, and even protein drugs, are much smaller than nanoparticles. Most drugs can diffuse all over the body. “But if we put the drug into a larger nanoparticle, we can keep it from spraying out over all the tissues,” detailed Heller.

His team also must consider how to deliver the nanoparticle containing the drug to a precise location in the tumor site, and whether there is a target that can lead it to that tumor site. “Most of the targets we are looking for are not on the tumor cells themselves, but on the blood vessels that are feeding the tumor,” said Heller. “Our targets are not drug targets, but rather gateways to the tumor, molecules on blood vessels in tumors sites, or sites of inflammation. Then we make sure that the nanoparticle has a molecule on the outside of it that can stick to those targets.”

The research takes the engineering team into the realms of vascular biology, vascular transport, and an understanding of how materials can get across the blood, across the blood/brain barrier, across the tumor barrier. “We are also exploring signaling pathways,” said Heller. “When trying to deliver a kinase inhibitor, for example, we must consider the target we are hitting, where else that target is in the body, and if there any other off-target proteins elsewhere in the body that the drug will hit. We also have to think about resistance mechanisms and compensatory pathways. So as a team we have been learning a lot of physiology.”

Heller says his 5-year-old laboratory contains requisite benches, a tissue culture room, and a studio equipped with lasers and optics for work on sensors. In the basement reside the all-important mice, critical to preclinical development and testing. Looking at target proteins in the body of a mouse, the team is able to determine if a drug encased in a nanoparticle hits the target, if it works better in a nanoparticle, and if it has the same side effects.

The eventual goal is to translate this understanding and these emerging technologies to clinical use and human patients. But it is a long row to hoe. “Once a technology is developed, it must go through the full ‘investigational new drug’ FDA process,” Heller lamented. “Even if a known compound is inside the particle, the whole particle is treated as a new drug.

That means we can’t just give it to clinicians to trial in patients; first the FDA must allow us to start a clinical trial.” Though regulatory delays are a frustration, the researcher said enthusiasm remains high because the potential of the new technologies is so powerful.

Back to Top | Article Outline

Nanoparticles in Detection

The Cancer Nanomedicine Laboratory also maintains an interest in developing innovative approaches to cancer detection that is “… easier and more predictive. We found that we can detect some cancers earlier by measuring certain biomarkers in a person without having to take blood or biofluids to do it,” said Heller.

Instead, a tiny sensor made of carbon nanotubes is inserted inside a person. The nanotubes give off infrared light that can pass through tissues. “We can implant nanomaterial in a body, shoot light into it from outside the body, and then get a reading externally,” detailed Heller. “These nanomaterials are very sensitive to certain stimuli. We can put an antibody onto the surface of the nanotube and when it binds to an antigen we can see a signal change—a shift in the wavelength of the nanotube fluorescence—through the tissue.” (The team successfully detected ovarian cancer signaling changes in a mouse model. This work was detailed in a paper, Non-Invasive Ovarian Cancer Biomarker Detection via an Optical Nanosensor Implant, coauthored by Heller in Science Advances [2018;4(4):eaaq1090]).

Implications for future use of this technology in humans are significant. Heller said the first possible application could be in people with risk factors for certain diseases. “We could implant a biomarker or panel of biomarkers in people to detect early stage cancer, to measure cancer recurrence, or to monitor treatment and have earlier warning when therapy stops working.”

Asked how early the signaling changes would become apparent, Heller said it depends on the level of a given marker in the tissue. “With ovarian cancer, we would look at the technology as an intrauterine device, placed near the source of the cancer. If we were to wait for biomarkers to reach a high enough level to be detected in the blood, we likely would be dealing with late-stage cancer. If we can measure that biomarker right next to the ovaries or fallopian tube, we would see signal changes at an even earlier point in the life cycle of the cancer.”

Looking downstream of this work, Heller said the team is already questioning if it might be possible to insert a small sensor under the skin, in the blood, or even in a tattoo to measure all kinds of biomarkers, then report a whole panel in real time, at early stages, back to a wearable Fitbit-like device. “The long-term hope is to find super easy ways to measure lots of biomarkers in real time,” said Heller.

Back to Top | Article Outline

Nanoparticles in Discovery

A third aspect of the work underway in Heller’s lab focuses on making research tools, specifically using carbon nanotubes as sensors in drug discovery assays. Heller believes the sensors will be able to measure things that have not been measurable before, or measured in ways that could not be accomplished before, such as in living cells and living tissue. “By measuring an analyte inside living cells or living tissue in mice, we gain the ability to do studies that cannot be done otherwise. This will allow us to address new hypotheses, and it will be helpful for drug development and for basic researchers at institutions such as MSKCC.”

Heller stressed that it is exactly institutions like MSKCC that can lead the way in helping biomedical engineers interact more fully with biomedical researchers. “Even though both of these concepts have the word ‘biomedical’ in them, ‘biomedical engineering’ departments come from engineering schools, while ‘biomedical research’ comes from places that often do not have engineering schools.

So there is a disconnect,” said Heller. “I realize how valuable it is to me as an engineering researcher to be in a biomedical institution and come in contact with the people who study biomedical questions and understand the medical problems. Biomedical institutions would benefit greatly from organized efforts to bring in engineering researchers whose goal it is to understand and make new technologies to address their problems.”

Heller laughed at the suggestion that some of the things he makes sound like cinematic props from the vintage sci-fi flick, The Incredible Voyage. “Sometimes people think we are the science fiction lab of Memorial Sloan Kettering,” he admitted with humor. And when asked if the younger history student/middle school teacher/or physical scientist in him ever thinks, “I can’t believe I am doing this kind of stuff,” he answered without hesitation, “Yeah, all the time. I think I have gotten to where I am by not defining myself. It’s important to be flexible. Where does it stop? It doesn’t. If you keep changing you can aspire to do anything you want.”

Valerie Neff Newitt is a contributing writer.

New Targeting strategy developed by Penn State may open door to better cancer drug delivery


Drug delivery targetingstrIn the transition from benign to malignant, cancer cells transition from stiff to soft. Mechanotargeting harnesses mechanics to improve targeting efficiency of nanparticle-based therapeutic agents. Credit: Zhang lab/vecteezy.com

Bioengineers may be able to use the unique mechanical properties of diseased cells, such as metastatic cancer cells, to help improve delivery of drug treatments to the targeted cells, according to a team of researchers at Penn State.

Many labs around the world are developing nanoparticle-based,  to selectively target tumors. They rely on a key-and-lock system in which protein keys on the surface of the nanoparticle click into the locks of a highly expressed protein on the surface of the cancer cell. The cell membrane then wraps around the nanoparticle and ingests it. If enough of the nanoparticles and their drug cargo is ingested, the cancer cell will die.

The adhesive force of the lock and key is what drives the nanoparticle into the cell, said Sulin Zhang, professor of engineering science and mechanics.

“It is almost universal that whenever there is a driving force for a process, there always is a resistive force,” Zhang said. “Here, the driving force is biochemical—the protein-protein interaction.”

The resistive force is the mechanical energy cost required for the membrane to wrap around the nanoparticle. Until now, bioengineers only considered the driving force and designed nanoparticles to optimize the chemical interactions, a targeting strategy called “chemotargeting.” Zhang believes they should also take into account the mechanics of the  to design nanoparticles to achieve enhanced targeting, which forms a new targeting strategy called “mechanotargeting.”

“These two targeting strategies are complementary; you can combine chemotargeting and mechanotargeting to achieve the full potential of nanoparticle-based diagnostic and therapeutic agents,” Zhang said. “The fact is that targeting efficiency requires a delicate balance between driving and resistive forces. For instance, if there are too many keys on the nanoparticle surface, even though these keys only weakly interact with the nonmatching locks on normal cells, these weak, off-target interactions may still provide enough adhesion energy for the nanoparticles to penetrate the  and kill the healthy cells.”

On the other hand, if the adhesion energy is not high enough, the nanoparticle won’t get into the cell.

In “Mechanotargeting: Mechanics-dependent Cellular Uptake of Nanoparticles,” published online ahead of print in the journal Advanced Materials, Zhang and the team report the results of experiments on cancer cells grown on hydrogels of variable stiffness. On soft hydrogels the cells remained cohesive and benign and experienced a nearly constant stress that limited the uptake of the nanoparticles. But on stiff hydrogels the cells became metastatic and adopted a three-dimensional shape, offering more surface area for nanoparticles to adhere, and became less stressed. Under this condition, the cells took up five times the number of nanoparticles as the benign cells.

“The nanoparticles are fluorescent, so we count the number of  that get into the cell by the fluorescence intensity. We found that in the malignant cells the intensity is five times higher,” Zhang said. “That proves that mechanotargeting works.”

 Explore further: Nanoparticle aggregates for destruction of cancer cells

More information: Qiong Wei et al, Mechanotargeting: Mechanics-Dependent Cellular Uptake of Nanoparticles, Advanced Materials (2018). DOI: 10.1002/adma.201707464

 

The University of Texas at Arlington has successfully patented (Europe) an implantable medical device that attracts and kills circulating cancer cells


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The University of Texas at Arlington has successfully patented in Europe an implantable medical device that attracts and kills circulating cancer cells that was invented by a faculty member. This cancer trap can be used for early diagnosis and treatment of metastasized cancer.

“Our cancer trap works just like a roach motel, where you put in some bait and the roach goes there and dies,” said Liping Tang, UTA bioengineering professor and leader of the research. “We are putting biological agents in a cancer trap to attract and kill cancer cells.

“This method is effective for both diagnosing and treating metastasis cancer and can be used in combination with traditional chemotherapy and radiation therapy,” he added.

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Currently, there are many treatments for primary tumors but they do little to prevent metastasis and stray cancer cells from relocating to another part of the body. Surgical removal of cancerous tissue also can spur the spread of cancer in the body. While there are drugs given to patients after surgery to prevent cancer cells from adhering to each other or other tissues, these drugs do not rid the body of cancer cells or collect them to allow an assessment of the patient’s status.

“We have made a nano-sized device that we can put under the skin using an injection needle to recruit the cancer cells into a small area where we can treat them with less overall side effects to the whole body,” Tang said.

“So the cancer trap is really complementary to current cancer treatments and especially beneficial at the early stages when it is difficult to see if the cancer is spreading as there are few cancer cells. We have also found it very effective in late stage cancers to stop the spread of the disease and to prolong lifespan,” he added.

The cancer trap works by releasing different chemokines or regulatory proteins to attract circulating cancer cells and then expose them to chemotherapeutic agents to eradicate potential spreading. The trap has been tested in the lab and proved effective on many kinds of cancer cells, including melanoma, prostate cancer, breast cancer, lung cancer, leukemia and esophageal cancer.

“We are hoping to move toward clinical trials in the next few years as this technology could potentially significantly increase the lifespan of cancer patients,” Tang said.

This work on cancer forms part of a larger program at UTA where more than 30 faculty from different colleges and disciplines are developing new solutions to attack this disease.

With more than $4 million in research expenditures in 2017, UTA’s program for cancer encompasses basic cancer research, identification and diagnostics, as well as in noninvasive, midterm, invasive and postoperative therapies. UTA’s multidisciplinary research teams harness proficiencies from across science, engineering, computer science, nursing and kinesiology to tackle the challenges of precision oncology and cancer treatment.

Tang’s expertise encompasses a broad area, including stem cells, tissue engineering, nanotechnology, biocompatibility, biomaterials, inflammation, infection and fibrosis. He has published many of his work in high impact journals, including BiomaterialsJournal of Clinical InvestigationProceedings of the National Academy of SciencesBloodJournal of Experimental Medicine, and Tissue Engineering.

“Tang is a remarkable innovator and internationally recognized researcher,” said Michael Cho, UTA’s chair of bioengineering. “His work is a clear example of UTA’s strategic focus on health and the human condition and of the strength of multidisciplinary work.”

Source

New Simple Blood Test can Detect Alzheimer’s 30 Years in Advance + Can Also Detect 8 Cancers: Videos


New Simple Blood Test can Detect Alzheimer’s 30 Years in Advance + Can Also Detect 8 Cancers

#GreatThingsFromSmallThings

Watch the Videos Below

Detecting Alzheimer’s 30 Years in Advance

8 Cancers Detected with ONE Simple Blood Test

Remote-control shoots laser at nano-gold to turn on cancer-killing immune cells – could one day send immune cells on a rampage against a malignant tumor


Nano Thermo Cancer 55092A heat-sensitive gene switch implanted in a sample of T-cells works in an in vitro check. Gentle pulses from a near-infrared laser directed at gold nanoparticles, which are also in the sample with the T-cells, transform into gentle heat and flip the switch on, activating the T-cells. The resulting signal appears as orange dots on a monitor in the background. CREDIT Georgia Tech / Allison Carter

Abstract:
A remote command could one day send immune cells on a rampage against a malignant tumor. The ability to mobilize, from outside the body, targeted cancer immunotherapy inside the body has taken a step closer to becoming reality.

Remote-control shoots laser at nano-gold to turn on cancer-killing immune cells

Bioengineers at the Georgia Institute of Technology have installed a heat-sensitive switch into T-cells that can activate the T-cells when heat turns the switch on. The method, tested in mice and published in a new study, is locally targeted and could someday help turn immunotherapy into a precision instrument in the fight against cancer.

Immunotherapy has made headlines with startling high-profile successes like saving former U.S. President Jimmy Carter from brain cancer. But the treatment, which activates the body’s own immune system against cancer and other diseases, has also, unfortunately, proved to be hit-or-miss.

“In patients where radiation and traditional chemotherapies have failed, this is where T-cell therapies have shined, but the therapy is still new,” said principal investigator Gabe Kwong. “This study is a step toward making it even more effective.”

Laser, gold, and T-cells

In the study, Kwong’s team successfully put their remote-control method through initial tests in mice with implanted tumors (so-called tumor phantoms, specially designed for certain experiments). The remote works via three basic components.

First, the researchers modified T-cells, a type of white blood cell, to include a genetic switch that, when switched on, increased the cells’ expression of specific proteins by more than 200 times. That ability could be used to guide T-cells’ cancer-fighting activities.

The T-cells, with the switch off, were introduced into the tumor phantom which was placed into the mice. The tumor phantom also included gold nanorods, just dozens of atoms in size. The researchers shone pulses of a gentle laser in the near-infrared (NIR) range from outside the mouse’s body onto the spot where the tumor was located.

The nanorods receiving the light waves turned them into useful, localized mild heat, allowing the researchers to precisely warm the tumor. The elevated heat turned on the T-cells’ engineered switch.

Hyper-activated T-cells

This study honed the method and confirmed that its components worked in living animals. It was not the intention of the study to treat cancer yet, although undertaking that is the next step, which is already on its way.

“In upcoming experiments, we are implementing this approach to treat aggressive tumors and establish cancer-fighting effectiveness,” said Kwong, who is an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

The researchers published their results in the current edition of the journal ACS Synthetic Biology. The study’s first author was graduate research assistant Ian Miller. The research was funded by the National Institutes of Health, the National Science Foundation, the Burroughs Wellcome Fund, and the Shurl and Kay Curci Foundation.

Better immunotherapy

Bioengineers have been able to do a lot with T-cells already when they’re outside of the body.

“Right now, we’re adept at harvesting a patient’s own T-cells, modifying to target cancer, growing them outside the body until there are hundreds of millions of them,” Kwong said. “But as soon as we inject them back into a patient, we lose control over the T-cells’ activity inside the body.”

Cancer is notoriously wily, and when T-cells crawl into a tumor, the tumor tends to switch off the T-cells’ cancer-killing abilities. Researchers have been working to switch them back on.

Kwong’s remote control has done this in the lab, while also boosting T-cell activity.

T-cell toxicities

Having an off-switch is also important. If T-cells were engineered to be always-on and hyper-activated, as they moved through the body, they could damage healthy tissue.

“There would be off-target toxicities, so you really want to pinpoint their activation,” Kwong said. “Our long-term goal for them is to activate site-specifically, so T-cells can overcome immunosuppression by the tumor and become better killers there.”

When the heat remote is turned off, so are Kwong’s engineered T-cells, because customary body temperatures are not high enough to activate their switch.

Heat-shock switch

The switch is a natural safety mechanism in human cells that has evolved to protect against heat shock and turns on when tissue temperatures rise above the body’s normal operating range, which centers on 37 degrees Celsius (98.6 F). But the researchers re-fitted T-cells with the switch to make it turn on other functions, and it could be used to hyper-activate the cells.

The Georgia Tech bioengineers found that the switch worked in a range of 40 to 42 degrees Celsius (104 – 107.6 F), high enough to not react to the majority of high fevers and low enough to not damage healthy tissue nor the engineered T-cells.

“When the local temperature is raised to 45 degrees (113 F), some cells in our body don’t like it,” Kwong said. “But if heating is precisely controlled in a 40 to 42 degrees window with short pulses of the NIR light, then it turns on the T-cells’ switch, and body cells are still very comfortable.”

Immuno-goals and dreams

The researchers want to combine the switch with some additional cancer-fighting weapons they envision engineering into T-cells.

For example, secreted molecules called cytokines can boost immune cells’ ability to kill cancer, but cytokines, unfortunately, can also be toxic. “Our long-term goal is to engineer T-cells to make and release powerful immune system stimulants like cytokines on command locally and sparingly,” Kwong said.

In other studies, gently heated gold nanorods have been shown to kill tumors or hinder metastasis. But T-cell treatments could be even more thorough and, in addition, hopefully, one day give patients treated with them a long-lasting memory immune response to any recurrence of their cancer.

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Citation: This experimental method is in laboratory stages in mice and is not yet available as a treatment of any type for human patients. The study was co-authored by Marielena Castro, Joe Maenza and Jason Weis of Coulter BME at Georgia Tech. The research was funded by the National Institutes of Health Director’s New Innovator Award (grant #DP2HD091793), the NIH National Center for Advancing Translational Sciences (grant #UL1TR000454), the NIH GT BioMAT Training Grant (#5T32EB006343), the National Science Foundation (grant # DGE-1451512), the Shurl and Kay Curci Foundation, and the Burroughs Wellcome Fund. Any findings or opinions are those of the authors and not necessarily of the funding agencies.

Novel Nanomedicine Inhibits Progression of Pancreatic Cancer in Mice – Tel Aviv University


Nanomedicine I download

Survival rates in pancreatic cancer linked to inverse correlation between specific oncogene and tumor suppressant, Tel Aviv University researchers say

A new Tel Aviv University study pinpoints the inverse correlation between a known oncogene — a gene that promotes the development of cancer — and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival. The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.

Nanomedicine III imagesThe study, which was published in Nature Communications, was led by Prof. Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine, and conducted by Hadas Gibori and Dr. Shay Eliyahu, both of Prof. Satchi-Fainaro’s multidisciplinary laboratory, in collaboration with Prof. Eytan Ruppin of TAU’s Computer Science Department and the University of Maryland and Prof. Iris Barshack and Dr. Talia Golan of Chaim Sheba Medical Center, Tel Hashomer.

Pancreatic cancer is among the most aggressive cancers known today. The overwhelming majority of pancreatic cancer patients die within just a year of diagnosis. “Despite all the treatments afforded by modern medicine, some 75% of all pancreatic cancer patients die within 12 months of diagnosis, including many who die within just a few months,” Prof. Satchi-Fainaro says.

“But around seven percent of those diagnosed will survive more than five years. We sought to examine what distinguishes the survivors from the rest of the patients,” Prof. Satchi-Fainaro continues. “We thought that if we could understand how some people live several years with this most aggressive disease, we might be able to develop a new therapeutic strategy.”

Nanomedicine I downloadCalling a nano-taxi

The research team examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumor suppressant, and PLK1, a known oncogene. The levels of miR-34a were low in pancreatic cancer mouse models, while the levels of the oncogene were high. This correlation made sense for such an aggressive cancer. But the team needed to see if the same was true in humans.

The scientists performed RNA profiling and analysis of samples taken from pancreatic cancer patients. The molecular profiling revealed the same genomic pattern found earlier in mouse models of pancreatic cancer.

The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumor and prevents side effects in surrounding healthy tissues.

“We designed a nanocarrier to deliver two passengers: (1) miR-34a, which degrades hundreds of oncogenes; and (2) a PLK1 small interfering RNA (siRNA), that silences a single gene,” Prof. Satchi-Fainaro says. “These were delivered directly to the tumor site to change the molecular signature of the cancer cells, rendering the tumor dormant or eradicating it altogether.Nanomedicine II pancreatic-cancer-1140x641

“The nanoparticle is like a taxi carrying two important passengers,” Prof. Satchi-Fainaro continues. “Many oncology protocols are cocktails, but the drugs usually do not reach the tumor at the same time. But our ‘taxi’ kept the ‘passengers’ — and the rest of the body — safe the whole way, targeting only the tumor tissue. Once it ‘parked,’ an enzyme present in pancreatic cancer caused the carrier to biodegrade, allowing the therapeutic cargo to be released at the correct address — the tumor cells.”

Improving the odds

To validate their findings, the scientists injected the novel nanoparticles into pancreatic tumor-bearing mice and observed that by balancing these two targets — bringing them to a normal level by increasing their expression or blocking the gene responsible for their expression — they significantly prolonged the survival of the mice.

“This treatment takes into account the entire genomic pattern, and shows that affecting a single gene is not enough for the treatment of pancreatic cancer or any cancer type in general,” according to Prof. Satchi-Fainaro.

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Research for the study was funded by the European Research Council (ERC), Tel Aviv University’s Cancer Biology Research Center (CBRC) and the Israel Science Foundation (ISF).

American Friends of Tel Aviv University (AFTAU) supports Israel’s most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. For three years in a row, TAU ranked 9th in the world, and first in Israel, for alumni going on to become successful entrepreneurs backed by significant venture capital, a ranking that surpassed several Ivy League universities. To date, 2,400 patents have been filed out of the University, making TAU 29th in the world for patents among academic institutions.