Copper-based Nanomaterials can KILL Cancer Cells in Mice


Cancer cell during cell division. Credit: National Institutes of Health

An interdisciplinary team of scientists from KU Leuven, the University of Bremen, the Leibniz Institute of Materials Engineering, and the University of Ioannina has succeeded in killing tumour cells in mice using nano-sized copper compounds together with immunotherapy. After the therapy, the cancer did not return.

Recent advances in  therapy use one’s own immunity to fight the cancer. However, in some cases, immunotherapy has proven unsuccessful.

The team of biomedical researchers, physicists, and chemical engineers found that tumours are sensitive to copper oxide nanoparticles—a compound composed of copper and oxygen. Once inside a living organism, these nanoparticles dissolve and become toxic.

By creating the nanoparticles using iron oxide, the researchers were able to control this process to eliminate , while healthy cells were not affected.

“Any material that you create at a nanoscale has slightly different characteristics than its normal-sized counterpart,” explain Professor Stefaan Soenen and Dr. Bella B. Manshian from the Department of Imaging and Pathology, who worked together on the study.

“If we would ingest  in large quantities, they can be dangerous, but at a nanoscale and at controlled, safe, concentrations, they can actually be beneficial.”

As the researchers expected, the cancer returned after treating with only the nanoparticles. Therefore, they combined the nanoparticles with immunotherapy. “We noticed that the copper compounds not only could kill the tumour cells directly, they also could assist those cells in the  that fight foreign substances, like tumours,” says Dr. Manshian.

The combination of the nanoparticles and immunotherapy made the tumours disappear entirely and, as a result, works as a vaccine for lung and colon cancer—the two types that were investigated in the study. To confirm their finding, the researchers injected tumour cells back into the mice. These cells were immediately eliminated by the immune system, which was on the lookout for any new, similar, cells invading the body.

The authors state that the novel technique can be used for about sixty percent of all cancers, given that the cancer cells stem from a mutation in the p53 gene. Examples include lung, breast, ovarian, and colon cancer.

A  is that the tumours disappeared without the use of chemotherapy, which typically comes with major side-effects. Chemotherapeutic drugs not only attack cancer cells, they often damage healthy cells along the way.

For example, some of these drugs wipe out white blood cells, abolishing the immune system.

“As far as I’m aware, this is the first time that metal oxides are used to efficiently fight cancer  with long-lasting immune effects in live models,” Professor Soenen says. “As a next step, we want to create other metal , and identify which particles affect which types of cancer. This should result in a comprehensive database.”

The team also plans to test  derived from cancer patient tissue. If the results remain the same, Professor Soenen plans to set up a clinical trial. For that to happen, however, there are still some hurdles along the way.

He explains: “Nanomedicine is on the rise in the U.S. and Asia, but Europe is lagging behind. It’s a challenge to advance in this field, because doctors and engineers often speak a different language. We need more interdisciplinary collaboration, so that we can understand each other better and build upon each other’s knowledge.”

More information: 
Hendrik Naatz et al, Model-Based Nanoengineered Pharmacokinetics of Iron-Doped Copper Oxide for Nanomedical Applications, Angewandte Chemie International Edition (2019).  DOI: 10.1002/anie.201912312

Journal information: Angewandte Chemie International Edition

Provided by KU Leuven

Study finds Salt Nanoparticles (Sodium Chloride or SCNP’s) are Toxic to Cancer Cells – University of Georgia


A new study at the University of Georgia has found a way to attack cancer cells that is potentially less harmful to the patient.

Sodium chloride nanoparticles—more commonly known as salt—are toxic to cancer cells and offer the potential for therapies that have fewer negative side effects than current treatments.

Led by Jin Xie, associate professor of chemistry, the study found that SCNPs can be used as a Trojan horse to deliver ions into cells and disrupt their internal environment, leading to cell death. SCNPs become salt when they degrade, so they’re not harmful to the body.

“This technology is well suited for localized destruction of cancer cells,” said Xie, a faculty member in the Franklin College of Arts and Sciences. “We expect it to find wide applications in treatment of bladder, prostate, liver, and head and neck cancer.”

Nanoparticles are the key to delivering SCNPs into cells, according to Xie and the team of researchers. Cell membranes maintain a gradient that keeps relatively low sodium concentrations inside cells and relatively high sodium concentrations outside cells.

The plasma membrane prevents sodium from entering a cell, but SCNPs are able to pass through because the cell doesn’t recognize them as sodium ions.

Once inside a cell, SCNPs dissolve into millions of sodium and chloride ions that are trapped inside by the gradient and overwhelm protective mechanisms, inducing rupture of the plasma membrane and cell death. When the plasma membrane ruptures, the molecules that leak out signal the immune system that there’s tissue damage, inducing an inflammatory response that helps the body fight pathogens.

“This mechanism is actually more toxic to cancer cells than normal cells, because cancer cells have relatively high sodium concentrations to start with,” Xie said.

Using a mouse model, Xie and the team tested SCNPs as a potential cancer therapeutic, injecting SCNPs into tumors. They found that SCNP treatment suppressed tumor growth by 66 percent compared to the control group, with no drop in body weight and no sign of toxicity to major organs.

They also performed a vaccination study, inoculating mice with cancer cells that had been killed via SCNPs or freeze thaw. These mice showed much greater resistance to a subsequent live cancer cell challenge, with all animals remaining tumor free for more than two weeks.

The researchers also explored anti-cancer immunity in a tumor model. After injecting primary tumors with SCNPs and leaving secondary tumors untreated, they found that the secondary tumors grew at a much lower speed than the control, showing a tumor inhibition rate of 53 percent.

Collectively, the results suggest that SCNPs killed cancer cells and converted the dying cancer cells to an in situ vaccine.

SCNPs are unique in the world of inorganic particles because they are made of a benign material, and their toxicity is based on the nanoparticle form, according to Xie.

“With a relatively short half-life in aqueous solutions, SCNPs are best suited for localized rather than systemic therapy. The treatment will cause immediate and immunogenic cancer cell death,” he said. “After the treatment, the nanoparticles are reduced to salts, which are merged with the body’s fluid system and cause no systematic or accumulative toxicity. No sign of systematic toxicity was observed with SCNPs injected at high doses.”

The study was published in Advanced Materials.

Are ‘NANOBOTS’ Helping Us Win the War Against Cancer?


Nanobots_Body-1296x729-Header

Nanomedicine researchers have successfully programmed nanorobots to find tumors and cut off their blood supply while leaving healthy tissue unharmed.

While we are living in an unprecedented level of digital disruption, we still face significant threats and challenges to our health and livelihoods. Everything from intensifying hurricanes due to climate change and increasing levels of income inequality will likely be issues that we confront in the decades to come. However, nanobots are perhaps not the most known digital innovations of this era, but they will become more and more visible now, especially considering cancer treatment!

Another key challenge that we face today is finding cures to devastating diseases—specifically cancer. The statistics are grim and researchers all around the world are working hard to find a way to develop a cure for cancer. While we aren’t quite there yet, one promising technology that may be able to help cure cancer are nanobots.

Nanobots are extremely exciting pieces of technology that are already being used for cancer treatment. Yes, the jury is still out on whether nanorobotics will become a cheap, yet extremely effective way to treat grave illnesses. Nevertheless, this is a technology that is certainly worth monitoring in the years to come and cancer will have a new enemy which is called nanobots.

NANOBOTS: A BRIEF DESCRIPTION

As a basic starting point, nanobots are tiny devices (ranging in size from 0.1 to 10 micrometers) that are constructed out of nanoscale or molecular components. For the sake of comparison, a red blood cell is approximately 0.1 to 10 micrometers. The essential idea of nanorobotics (nanobots) is that these tiny devices carry out certain procedures and instructions to solve a certain problem—all at an extremely small scale. To put it another way, nanobots are machines that can build and manipulate things with an extremely high degree of precision at an atomic level.

Some of the potential applications of nanobots include medical imaging, information storage devices, smart windows and walls, and even connecting our brains to the Internet. Already, researchers have already made several significant advancements in the technical aspects of nanorobotics. For example, several different groups of researchers have developed a “high-speed, remote-controlled nanoscale version of a rocket by combining nanoparticles with biological molecules.” Physicists from the University of Mainz have developed the so-called “smallest engine ever created” from a solitary atom. For more details on these (and other) advancements, click here.

TAKING THE FIGHT TO CANCER

We are still in the early days of nanorobotics, yet we have already seen the promise of nanobots being used to treat cancer. One of the most exciting studies came from researchers from Arizona State University and the National Center for Nanoscience and Technology of the Chinese Academy of Sciences. These researchers injected nanobots into the bloodstream of mice, and these nanobots targeted blood vessels around cancerous tumors. The nanobots, by using their embedded blood clotting drugs to cut off these blood vessels’ blood supply, were able to shrink the tumors and inhibit their spread. They were able to precisely target cancerous tumors and do it much more effectively than a surgeon with a scalpel ever could.

Another study from earlier this year used a DNA nanorobot that successfully sought out breast cancer cells in mice and targeted a specific protein. The researchers used nanobots to lower levels of a protein called human epidermal growth factor receptor 2 (HER2), which helps cancer cells proliferate uncontrollably. While the nanobot would need significantly more improvement before widespread use, it is yet another promising illustration of nanobots being used to treat cancer.

WHAT LIES AHEAD

Nanorobotics is tremendously exciting. That said, whether they are being used to treat cancer or create smart windows and walls, researchers need to overcome some significant challenges. For instance, researchers are still trying to determine an effective way to get these minuscule robots to travel to (and stay) at certain points in the body. Nanobots also need to avoid being expelled from the body by things like toxic or foreign bodies.

Once again, we are still in early innings. Researchers are going to need to invest a large amount of time, energy, and money into overcoming these challenges. There is no guarantee that the potential applications of nanorobotics will be available in our day-to-day lives.

But that said, the potential is there. Researchers have already made some significant progress, and it is likely that more is on the way. Whether you work in an industry that may be disrupted by nanorobotics or are simply interested in the technology, the next few years will certainly be fascinating.

The Two Directions of Nanomedicine in the Treatment of Cancer


direction of cancer download

The cancer nanomedicine field is heading in two directions — debating whether the clinical translation of nanomaterials should be accelerated or whether some of the long-standing drug delivery paradigms have to be challenged first.

At the International Conference on Nanomedicine and Nanobiotechnology that was held in Munich, 16–18 October, the most striking talk was not given by a scientist, nor a clinician, but by Lora Kelly — a six-year pancreatic cancer survivor.

By telling her story of how it actually feels to receive chemotherapy, immunotherapy and radiation, she reminded everyone about the urgent need to improve cancer treatment regimes. The main goal remains to kill the cancer; however, it has become more evident how equally important it is to improve the quality of life of patients during treatment, that is, to reduce the often devastating side effects.

This is where nanomedicine comes in. Nanomaterials have the potential to direct drugs to specific tissues and to improve drug activity, as well as its transport in blood. Indeed, nanoparticles could ensure that therapeutic treatments act locally and not systemically, and thus improve anti-cancer efficacy while reducing damage to healthy tissues.

However, recent setbacks, including the bankruptcy of a prominent nanomedicine company1 and the less than 1% delivery efficiency claim2 (quoted at every cancer nanomedicine conference on at least one slide) have stirred discussions about the usefulness of nanomedicines for cancer treatment.

Some argue that the field is stuck in preclinical animal models owing to a lack of insight into the basics of nanomaterial–tissue interactions in the human body, from traversing biological barriers to clearance.

 

While less than 1% delivery efficiency might not be much, pharmacological parameters, such as peak drug concentration, clearance rate and elimination half-life, are often not as bad3, and these should be considered with equal importance.

Moreover, there are also clinical success stories of nanomedicines. Onpattro, a lipid nanoparticle-based short interfering RNA (siRNA) drug for the treatment of polyneuropathies, was approved by the US Food and Drug Administration in 2018, marking the first approved nanoparticle for nucleic acid delivery.

In a Comment in this issue, Akinc et al. report the endeavour of developing this nanomedicine, from the idea to preclinical and clinical testing4, to the final approval. There are further many opportunities for nanomaterials complementary to drug delivery, including bioimaging, modulation of the immune system and the tumour microenvironment, and, of course, local administration.

 

From an Editorial perspective, the ongoing discussion is reflected in the many manuscripts we receive, which often include both basic investigations and claims of clinical application. Naturally, this can lead to mixed peer-review reports echoing the disconnection between clinical vision and fundamental science.

Reviewers with a background in materials science or biomedical engineering often point out the gaps in the basic understanding of how a nanomaterial interacts with the biological environment, and clinicians would like to see more preclinical animal work. Indeed, a thorough fundamental study does not always need the claim of a specific application, as it might be exactly such overstatements that have precluded the field to deliver on the promise of revolutionizing drug delivery.

Along the same line, studies of nanoparticle transport through specific cells or nanomaterial–cell interactions at a molecular scale, do not necessarily require complex in vivo models; by contrast, applied studies claiming a therapeutic benefit need a robust in vivo validation in a relevant animal model — preferably with an intact immune system.

 

Going back to the goal of improving a patient’s life, possible side effects and impact on tissues other than tumours should also be reported. However, this data is often found, at best, somewhere in the supplementary information.

Regardless of the mouse model, the discussion rarely goes beyond the weight loss and the histology of organs. If the idea is to improve therapies, side effects need to be thoroughly investigated — even at an early preclinical stage. Similarly, we will make sure that studies claiming superiority of a therapeutic treatment compared to state-of-the-art treatment regimes are reviewed by clinical experts to ensure that clinical translation is — at least — possible and feasible.

Also, keeping regulatory requirements in mind, the more complex the new nanoparticle or nanoscale delivery agent, the more difficult it will be to get approval; and this is a valid criticism.

 

At Nature Nanotechnology, we consider both clinically relevant manuscripts and fundamental studies investigating the various barriers nanoparticles face on their journey through the body. We endeavour to assess the manuscripts we receive as fairly and consistently as possible, with the ongoing discussion in mind. We look forward to learning about possible alternative mechanisms and the heterogeneity of the enhanced permeability and retention (EPR) effect, nanoparticle interactions in the liver, spleen and kidneys during clearance, migration of nanomaterials through the tumour microenvironment, and nanoparticle uptake, lysosomal escape (or not) and transport in different cell types.

Such studies will shine a light on nanomaterial–tissue interactions, and also greatly contribute to the development of improved nanomedicines. Equally important, detailed investigations of nanoparticles in preclinical animal models as well as relevant organoid cultures will allow the optimization of treatment strategies and the reduction of side effects. Regardless of the aim, we urge authors to calibrate their claims in accordance with their data and scope of the investigation to preserve trust in cancer nanomedicine as a whole.

Monitoring Cancer at the Nano-Level – University of Waterloo


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Tapered nanowire array device design. Credit: Nature Nanotechnology (2019). DOI: 10.1038/s41565-019-0393-2

How a new quantum sensor could improve cancer treatment

The development of medical imaging and monitoring methods has profoundly impacted the diagnosis and treatment of cancer. These non-invasive techniques allow health care practitioners to look for cancer in the body and determine if treatment is working.

But current techniques have limitations; namely, tumours need to be a specific size to be visible. Being able to detect cancer cells, even before there are enough to form a tumour, is a challenge that researchers around the world are looking to solve.

The solution may lie in nanotechnology

Researchers at the University of Waterloo’s Institute for Quantum Computing (IQC) have developed a quantum sensor that is promising to outperform existing technologies in monitoring the success of cancer treatments.

Sensor image

 Artist’s rendering of the interaction of incident single photon pulses and a tapered semiconductor nanowire array photodetector.

 

“A sensor needs to be very efficient at detecting light,” explains principal investigator Michael Reimer, an IQC faculty member and professor in the Faculty of Engineering. “What’s unique about our sensor is that the light can be absorbed all the way, from UV to infrared. No commercially available device exists that can do that now.”

 

Current sensors reflect some of the light, and depending on the material, this reflection can add up to 30 percent of the light not being absorbed.

This next-generation quantum sensor designed in Reimer’s lab is very efficient and can detect light at the fundamental limit — a single photon — and refresh for the next one within nanoseconds. Researchers created an array of tapered nanowires that turn incoming photons into electric current that can be amplified and detected.

When applied to dose monitoring in cancer treatment, this enhanced ability to detect every photon means that a health practitioner could monitor the dose being given with incredible precision — ensuring enough is administered to kill the cancer cells, but not too much that it also kills healthy cells.

Moving quantum technology beyond the lab

Reimer published his findings in Nature Nanotechnology in March and is now working on a prototype to begin testing outside of his lab. Reimer’s goal is to commercialize the sensor in the next three to five years.

“I enjoy the fundamental research, but I’m also interested in bringing my research out of the lab and into the real world and making an impact to society,” says Reimer.

He is no stranger to bringing quantum technology to the marketplace. While completing his post doctorate at the Delft University of Technology in The Netherlands, Reimer was an integral part of the startup, Single Quantum, developing highly efficient single-photon detectors based on superconducting nanowires.

Reimer’s latest sensor has a wide range of applications beyond dose monitoring for cancer treatments. The technology also has the ability to significantly improve high-speed imaging from space and long-range, high-resolution 3D images.

“A broad range of industries and research fields will benefit from a quantum sensor with these capabilities,” said Reimer. “It impacts quantum communication to quantum lidar to biological applications. Anywhere you have photon-starved situations, you would want an efficient sensor.”

He is exploring all industries and opportunities to put this technology to use.

Breakthroughs come in unexpected places

After earning his undergraduate degree in physics at the University of Waterloo, Reimer moved to Germany to play professional hockey. While taking graduate courses at the Technical University of Munich, he met a professor of nanotechnology who sparked his interest in the field.

“I played hockey and science was my hobby,” says Reimer. “Science is still my hobby, and it’s amazing that it is now my job.” Reimer went on to complete his PhD at the University of Ottawa/National Research Council of Canada, and turned his attention to quantum light sources. Reimer is an internationally renowned expert in quantum light sources and sensors. The idea for the quantum sensor came from his initial research in quantum light sources.

“To get the light out from the quantum light source, we had to come up with a way that you don’t have reflections, so we made this tapered shape. We realized that if we can get the light out that way we could also do the reverse — that’s where the idea for the sensor came from.”

Reimer will be at the Waterloo Innovation Summit on October 1, to present his latest breakthrough and its potential impact on the health care sector. And while he works to bring the sensor to market, Reimer’s lab continues to push the boundaries of quantum photonics.

From discovering the path to perfect photon entanglement to developing novel solid-state quantum devices, Reimer’s research is advancing technologies that could disrupt a multitude of industries and research fields.

Nanoparticles used to Transport Anti-Cancer Agent to Cells – University of Cambridge


Cancer transport 14-nanoparticle
Cells with MOFs carrying siRNA. Credit: University of Cambridge

Scientists from the University of Cambridge have developed a platform that uses nanoparticles known as metal-organic frameworks to deliver a promising anti-cancer agent to cells.

Research led by Dr. David Fairen-Jimenez, from the Cambridge Department of Chemical Engineering and Biotechnology, indicates  (MOFs) could present a viable platform for delivering a potent anti-cancer agent, known as siRNA, to .

Small interfering ribonucleic acid (siRNA), has the potential to inhibit overexpressed cancer-causing genes, and has become an increasing focus for scientists on the hunt for new cancer treatments.

Fairen-Jimenez’s group used computational simulations to find a MOF with the perfect pore size to carry an siRNA molecule, and that would breakdown once inside a cell, releasing the siRNA to its target. Their results were published today in Cell Press journal, Chem.

Some cancers can occur when  inside cells cause over-production of particular proteins. One way to tackle this is to block the gene expression pathway, limiting the production of these proteins.

SiRNA molecules can do just that—binding to specific gene messenger molecules and destroying them before they can tell the cell to produce a particular protein. This process is known as ‘gene knockdown’. Scientists have begun to focus more on siRNAs as potential cancer therapies in the last decade, as they offer a versatile solution to disease treatment—all you need to know is the sequence of the gene you want to inhibit and you can make the corresponding siRNA that will break it down. Instead of designing, synthesising and testing new drugs—an incredibly costly and lengthy process—you can make a few simple changes to the siRNA molecule and treat an entirely different disease.

One of the problems with using siRNAs to treat disease is that the molecules are very unstable and are often broken down by the cell’s natural defence mechanisms before they can reach their targets. SiRNA molecules can be modified to make them more stable, but this compromises their ability to knock down the target genes. It’s also difficult to get the molecules into cells—they need to be transported by another vehicle acting as a delivery agent.

Nanoparticles used to transport anti-cancer agent to cells
Crystalline metal-organic framework. Credit: David Fairen-Jimenez

The Cambridge researchers have used a special nanoparticle to protect and deliver siRNA to cells, where they show its ability to inhibit a specific target gene.

Fairen-Jimenez leads research into advanced materials, with a particular focus on MOFs: self-assembling 3-D compounds made of metallic and organic building blocks connected together.

There are thousands of different types of MOFs that researchers can make—there are currently more than 84,000 MOF structures in the Cambridge Structural Database with 1000 new structures published each month—and their properties can be tuned for specific purposes. By changing different components of the MOF structure, researchers can create MOFs with different pore sizes, stabilities and toxicities, enabling them to design structures that can carry molecules such as siRNAs into cells without harmful side effects.

“With traditional cancer therapy if you’re designing new drugs to treat the system, these can have different behaviours, geometries, sizes, and so you’d need a MOF that is optimal for each of these individual drugs,” says Fairen-Jimenez. “But for siRNA, once you develop one MOF that is useful, you can in principle use this for a range of different siRNA sequences, treating different diseases.”

“People that have done this before have used MOFs that don’t have a porosity that’s big enough to encapsulate the siRNA, so a lot of it is likely just stuck on the outside,” says Michelle Teplensky, former Ph.D. student in Fairen-Jimenez’s group, who carried out the research. “We used a MOF that could encapsulate the siRNA and when it’s encapsulated you offer more protection. The MOF we chose is made of a zirconium based metal node and we’ve done a lot of studies that show zirconium is quite inert and it doesn’t cause any toxicity issues.”

Using a biodegradable MOF for siRNA delivery is important to avoid unwanted build-up of the structures once they’ve done their job. The MOF that Teplensky and team selected breaks down into harmless components that are easily recycled by the cell without harmful side effects. The large pore size also means the team can load a significant amount of siRNA into a single MOF molecule, keeping the dosage needed to knock down the genes very low.

“One of the benefits of using a MOF with such large pores is that we can get a much more localised, higher dose than other systems would require,” says Teplensky. “SiRNA is very powerful, you don’t need a huge amount of it to get good functionality. The dose needed is less than 5% of the porosity of the MOF.”Structure-and-mechanism-of-siRNA-A-Structure-of-siRNA-B-Action-of-RNAi

MOFs or other vehicles to carry small molecules into cells is that they are often stopped by the cells on the way to their target. This process is known as endosomal entrapment and is essentially a defence mechanism against unwanted components entering the cell. Fairen-Jimenez’s team added extra components to their MOF to stop them being trapped on their way into the cell, and with this, could ensure the siRNA reached its target.

The team used their system to knock down a gene that produces fluorescent proteins in the cell, so they were able to use microscopy imaging methods to measure how the fluorescence emitted by the proteins compared between cells not treated with the MOF and those that were. The group made use of in-house expertise, collaborating with super-resolution microscopy specialists Professors Clemens Kaminski and Gabi Kaminski-Schierle, who also lead research in the Department of Chemical Engineering and Biotechnology.

Using the MOF platform, the team were consistently able to prevent gene expression by 27%, a level that shows promise for using the technique to knock down cancer genes.

Fairen-Jimenez believes they will be able to increase the efficacy of the system and the next steps will be to apply the platform to genes involved in causing so-called hard-to-treat cancers.

“One of the questions we get asked a lot is ‘why do you want to use a metal-organic framework for healthcare?’, because there are metals involved that might sound harmful to the body,” says Fairen-Jimenez. “But we focus on difficult diseases such as hard-to-treat cancers for which there has been no improvement in treatment in the last 20 years. We need to have something that can offer a solution; just extra years of life will be very welcome.”

The versatility of the system will enable the team to use the same adapted MOF to deliver different siRNA sequences and target different . Because of its large pore size, the MOF also has the potential to deliver multiple drugs at once, opening up the option of combination therapy.


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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.

Scientists develop novel nano-vaccine for melanoma


Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Credit: Wikipedia/CC BY-SA 3.0

Researchers at Tel Aviv University have developed a novel nano-vaccine for melanoma, the most aggressive type of skin cancer. Their innovative approach has so far proven effective in preventing the development of melanoma in mouse models and in treating primary tumors and metastases that result from melanoma.

The focus of the research is on a nanoparticle that serves as the basis for the new vaccine. The study was led by Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology and head of the Laboratory for Cancer Research and Nanomedicine at TAU’s Sackler Faculty of Medicine, and Prof. Helena Florindo of the University of Lisbon while on sabbatical at the Satchi-Fainaro lab at TAU; it was conducted by Dr. Anna Scomparin of Prof. Satchi-Fainaro’s TAU lab, and postdoctoral fellow Dr. João Conniot. The results were published on August 5 in Nature Nanotechnology.

Melanoma develops in the skin cells that produce melanin or skin pigment. “The war against cancer in general, and melanoma in particular, has advanced over the years through a variety of treatment modalities, such as chemotherapy, radiation therapy and immunotherapy; but the vaccine approach, which has proven so effective against various viral diseases, has not materialized yet against cancer,” says Prof. Satchi-Fainaro. “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  to immunotherapies.”

The researchers harnessed tiny particles, about 170 nanometers in size, made of a biodegradable polymer. Within each particle, they “packed” two peptides—short chains of amino acids, which are expressed in melanoma cells. They then injected the nanoparticles (or “nano-vaccines”) into a  bearing melanoma.

“The nanoparticles acted just like known vaccines for viral-borne diseases,” Prof. Satchi-Fainaro explains. “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. 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.”

The researchers then examined the effectiveness of the vaccine under three different conditions.

First, the vaccine proved to have prophylactic effects. The vaccine was injected into healthy mice, and an injection of melanoma  followed. “The result was that the mice did not get sick, meaning that the vaccine prevented the disease,” says Prof. Satchi-Fainaro.

Second, the nanoparticle was used to treat a primary tumor: A combination of the innovative vaccine and immunotherapy treatments was tested on melanoma model mice. The synergistic treatment significantly delayed the progression of the disease and greatly extended the lives of all treated mice.

Finally, the researchers validated their approach on tissues taken from patients with melanoma brain metastases. This suggested that the nano- can be used to treat brain metastases as well. Mouse models with late-stage melanoma brain metastases had already been established following excision of the primary melanoma lesion, mimicking the clinical setting. Research on image-guided surgery of primary melanoma using smart probes was published last year by Prof. Satchi-Fainaro’s lab.

“Our research opens the door to a completely new approach—the —for effective treatment of , even in the most advanced stages of the disease,” concludes Prof. Satchi-Fainaro. “We believe that our platform may also be suitable for other types of cancer and that our work is a solid foundation for the development of other cancer nano-vaccines.”

More information: Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators, Nature Nanotechnology(2019). DOI: 10.1038/s41565-019-0512-0 , https://nature.com/articles/s41565-019-0512-0

Journal information: Nature Nanotechnology

Provided by Tel Aviv University

Researchers at Oregon State University reach Milestone in use of Nanoparticles to kill Cancer with Heat


Abstract:
Researchers at Oregon State University have developed an improved technique for using magnetic nanoclusters to kill hard-to-reach tumors.

 

Magnetic nanoparticles – tiny pieces of matter as small as one-billionth of a meter – have shown anti-cancer promise for tumors easily accessible by syringe, allowing the particles to be injected directly into the cancerous growth.

Once injected into the tumor, the nanoparticles are exposed to an alternating magnetic field, or AMF. This field causes the nanoparticles to reach temperatures in excess of 100 degrees Fahrenheit, which causes the cancer cells to die.

But for some cancer types such as prostate cancer, or the ovarian cancer used in the Oregon State study, direct injection is difficult. In those types of cases, a “systemic” delivery method – intravenous injection, or injection into the abdominal cavity – would be easier and more effective.

The challenge for researchers has been finding the right kind of nanoparticles – ones that, when administered systemically in clinically appropriate doses, accumulate in the tumor well enough to allow the AMF to heat cancer cells to death.

Olena Taratula and Oleh Taratula of the OSU College of Pharmacy tackled the problem by developing nanoclusters, multiatom collections of nanoparticles, with enhanced heating efficiency. The nanoclusters are hexagon-shaped iron oxide nanoparticles doped with cobalt and manganese and loaded into biodegradable nanocarriers.

Findings were published in ACS Nano.

“There had been many attempts to develop nanoparticles that could be administered systemically in safe doses and still allow for hot enough temperatures inside the tumor,” said Olena Taratula, associate professor of pharmaceutical sciences. “Our new nanoplatform is a milestone for treating difficult-to-access tumors with magnetic hyperthermia. This is a proof of concept, and the nanoclusters could potentially be optimized for even greater heating efficiency.”

The nanoclusters’ ability to reach therapeutically relevant temperatures in tumors following a single, low-dose IV injection opens the door to exploiting the full potential of magnetic hyperthermia in treating cancer, either by itself or with other therapies, she added.

“It’s already been shown that magnetic hyperthermia at moderate temperatures increases the susceptibility of cancer cells to chemotherapy, radiation and immunotherapy,” Taratula said.

The mouse model in this research involved animals receiving IV nanocluster injections after ovarian tumors had been grafted underneath their skin.

“To advance this technology, future studies need to use orthotopic animal models – models where deep-seated tumors are studied in the location they would actually occur in the body,” she said. “In addition, to minimize the heating of healthy tissue, current AMF systems need to be optimized, or new ones developed.”

The National Institutes of Health, the OSU College of Pharmacy and Najran University of Saudi Arabia supported this research.

Also collaborating were OSU electrical engineering professor Pallavi Dhagat, postdoctoral scholars Xiaoning Li and Canan Schumann of the College of Pharmacy, pharmacy graduate students Hassan Albarqi, Fahad Sabei and Abraham Moses, engineering graduate student Mikkel Hansen, and pre-pharmacy undergrads Tetiana Korzun and Leon Wong.

Copyright © Oregon State University

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