Getting more Cancer-Fighting Nanoparticles to where they are Needed: University of Toronto


2-chemotherapyCredit: CC0 Public Domain

University of Toronto Engineering researchers have discovered a dose threshold that greatly increases the delivery of cancer-fighting drugs into a tumor.

Determining this threshold provides a potentially universal method for gauging nanoparticle dosage and could help advance a new generation of cancer therapy, imaging and diagnostics.

“It’s a very simple solution, adjusting the dosage, but the results are very powerful,” says MD/Ph.D. candidate Ben Ouyang, who led the research under the supervision of Professor Warren Chan.

Their findings were published today in Nature Materials, providing solutions to a drug- problem previously raised by Chan and researchers four years ago in Nature Reviews Materials.

Nanotechnology carriers are used to deliver drugs to cancer sites, which in turn can help a patient’s response to treatment and reduce , such as hair loss and vomiting. However, in practice, few injected particles reach the tumor site.

In the Nature Reviews Materials paper, the team surveyed literature from the past decade and found that on median, only 0.7 percent of the chemotherapeutic nanoparticles make it into a targeted tumor.

“The promise of emerging therapeutics is dependent upon our ability to deliver them to the target site,” explains Chan. “We have discovered a new principle of enhancing the delivery process. This could be important for nanotechnology, genome editors, immunotherapy, and other technologies.”

Chan’s team saw the liver, which filters the blood, as the biggest barrier to nanoparticle drug delivery. They hypothesized that the liver would have an uptake rate threshold—in other words, once the organ becomes saturated with nanoparticles, it wouldn’t be able to keep up with . Their solution was to manipulate the dose to overwhelm the organ’s filtering Kupffer cells, which line the liver channels.

The researchers discovered that injecting a baseline of 1 trillion nanoparticles in mice, in vivo, was enough to overwhelm the cells so that they couldn’t take up particles quick enough to keep up with the increased doses. The result is a 12 percent delivery efficiency to the tumor.

“There’s still lots of work to do to increase the 12 percent but it’s a big step from 0.7,” says Ouyang. The researchers also extensively tested whether overwhelming Kupffer cells led to any risk of toxicity in the liver, heart or blood.

“We tested gold, silica, and liposomes,” says Ouyang. “In all of our studies, no matter how high we pushed the dosage, we never saw any signs of toxicity.”

The team used this threshold principle to improve the effectiveness of a clinically used and chemotherapy-loaded nanoparticle called Caelyx. Their strategy shrank tumors 60 percent more when compared to Caelyx on its own at a set dose of the chemotherapy drug, doxorubicin.

Because the researchers’ solution is a simple one, they hope to see the threshold having positive implications in even current nanoparticle-dosing conventions for human clinical trials. They calculate that the human threshold would be about 1.5 quadrillion nanoparticles.

“There’s a simplicity to this method and reveals that we don’t have to redesign the  to improve delivery,” says Chan. “This could overcome a major delivery problem.”


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Researchers find more precise way to target tumours with anti-cancer drugs

Tiny Nanoparticles Offer Large Potential for Brain Cancer Treatment


tiny brain nanoparticles 1-tinynanopartFor patients with malignant brain tumors, the prognosis remains dismal. With the most aggressive treatments available, patients are usually only expected to live about 14 months after a diagnosis

This is because, chemotherapy, the most common form of treatment for cancer, is uniquely challenging for   patients. The delicate organ in our skulls is protected by a network of vessels and tissue called the blood-brain barrier that keeps most foreign substances out. Furthermore,  can cause significant damage to the rest of the body if they are not able to target the tumor in a pharmacologically significant dose.

These challenges have plagued scientists for years, but a team of researchers for Yale School of Medicine and Beijing Normal University just published a breakthrough study detailing a new method that offers a promise at treatment. The solution? Nanoparticles.

Nanoparticles, particles that are smaller than wavelengths of visible light and can only be seen under a special microscope, have the potential to pass through the blood-brain barrier. They can also carry drugs to targeted areas of the body, reducing the side effects on the rest of the body. But previous nanoparticles were very complex and not very efficient in penetrating in the brain.

This most recent paper, published in Nature Biomedical Engineering on March 30, 2020, describes a small carbon nanoparticle engineered by the two labs that could both deliver chemotherapy drugs across the blood-brain barrier and mark tumor cells with fluorescence in mice. What’s more, this nanoparticle is incredibly simple—made up of only one single compound.

“The major problems we’ve solved is to improve the delivery efficiency and specificity of nanoparticles,” says Jiangbing Zhou, Ph.D., associate Professor of Neurosurgery and of Biomedical Engineering at Yale School of Medicine. “We created nanoparticles like building a missile. There’s usually a GPS on every missile to guide it into a specific location and we’re able to guide particles to penetrate the brain and find tumors.”

The GPS-like targeting occurs because the nanoparticles engineered to be recognized by a molecule called LAT1, which is present in the blood-brain  as well as many tumors, but not in most other normal organs. As a result, chemotherapy drugs can be loaded on the dots and target tumors while barely affecting the rest of the body. The nanoparticles gain entry to the brain because they’ve been engineered to look like amino acids, which are allowed past the  as nutrients.

The nanoparticles have wider implications than  delivery. They can be stimulated to emit a fluorescence, which helps surgeons locate tumor to remove with greater accuracy.

Still, there’s a long road ahead before this research can be applied in a clinical setting, says Dr. Zhou. “It takes a long time before the technology can be translated into clinical applications,” he says. “But this finding suggests a new direction for developing  for drug delivery to the brain by targeting LAT1 molecules.”


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Improving drug delivery for brain tumor treatment


More information: Shuhua Li et al. Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids, Nature Biomedical Engineering (2020). DOI: 10.1038/s41551-020-0540-y

Journal information: Nature Biomedical Engineering

Unmasking a hidden killer: Successfully detecting cancer in blood of patients undergoing treatment


unmaskingahi
Dr Yuling Wang. Credit: CNBP

Pancreatic cancer is one of the most lethal cancers, but difficult to diagnose: few sufferers have symptoms until the cancer has become large or already spread to other organs. Even then, symptoms can be vague and easily misconstrued as more common conditions.

This is why Dr. Yuling Wang is so excited by results of a trial completed in late 2019, which—using plasmonic nanoparticles developed by the Centre for Nanoscale BioPhotonics (CNBP)—successfully detected signs of the  in  of patients undergoing treatment. The paper was recently published in the journal American Chemical Society—Sensors.

“The test gave a very high signal in the blood for late-stage or very serious tumors, where other techniques cannot detect anything,” said Dr. Wang, an associate investigator at the Centre’s Macquarie University node in Sydney, in work led by Prof Nicolle Packer. “We need to test many more patient samples to validate the approach, but the strength of the signal was very encouraging.”

They did this by developing a method, using surface-enhanced Raman spectroscopy nanotags, that simultaneously detects three known  cancer biomarkers in blood. Known as extracellular vesicles, or EVs, they contain DNA and proteins for cell-to-cell communication and are shed from pancreatic cancer cells into surrounding body fluids. The CNBP method zeros in on three: Glypican-1, epithelial cell adhesion molecules and CD44V6.

Unmasking a hidden killer

Non-invasive screening of cancer biomarkers from blood with handheld Raman reader. Credit: CNBP

For the experiment, biopsies of healthy donors were provided alongside those of known sufferers of pancreatic cancer, in double-blind tests where the researchers did not know which was which. Nevertheless, the blood of sufferers was easily identified. The technique was so sensitive it could spot EVs as small as 113 nanometres in diameter—or less than 1% the width of a human hair—in every millilitre of blood.

The pancreas is part of the digestive system, secreting insulin into the bloodstream to regulate the body’s sugar level as well as important enzymes and hormones into the  to help break down food. Pancreatic cancer is the fifth biggest cancer killer in Australia and has a 5-year survival rate of 8.7%. More than 3000 Australians are diagnosed annually, and surgery to remove the cancer is a long and complex process, requiring long hospital stays.

Because existing blood tests for the protein biomarkers of pancreatic cancer are unreliable, imaging with endoscopic ultrasound or MRI scans is necessary. Even then, anomalies can only be confirmed with a biopsy of the organ, which is invasive and ultimately relies on a trained pathologist to recognize signs of the cancer under a microscope. As a result, there’s some subjectivity involved and cancer can be present but still be missed.

“Our approach is non-invasive—we don’t need to take tissue from the patient, we just use a  to test blood for targeted biomarkers, which gives a very quick result,” Dr. Wang said. It may also help provide earlier diagnosis of the cancer.

While the work is a proof-of-concept, it was also able to detect colorectal and bladder cancer biomarkers—although not as clearly as those for . Nevertheless, the results are so encouraging that a commercial partner has committed funding to CNBP so it can develop a handheld spectrometer for cancer biomarkers in blood.


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Researchers develop technique to create nanomaterials which may help detect cancer earlier – U of Central Florida


37-researchersdAssistant Professor Xiaohu Xia works in his chemistry lab at the University of Central Florida. Credit: UCF, Karen Norum

For the first time, a team of scientists at the University of Central Florida has created functional nanomaterials with hollow interiors that can be used to create highly sensitive biosensors for early cancer detection.

Xiaohu Xia, an assistant professor of chemistry with a joint appointment in the NanoScience Technology Center, and his team developed the new method and recently published their work in the journal ACS Nano.

“These advanced hollow nanomaterials hold great potential to enable high-performance technologies in various areas,” says Xia. “Potentially we could be talking about a better and less expensive diagnostic tool, sensitive enough to detect biomarkers at low concentrations, which could make it invaluable for early detection of cancers and infectious diseases.”

Because hollow nanomaterials made of gold and silver alloys display superior optical properties, they could be particularly good for developing better  strip technology, similar to over-the-counter pregnancy tests. Currently the technology used to indicate positive or negative symbols on the test stick is not sensitive enough to pick up markers that indicate certain types of cancer. But Xia’s new method of creating hollow nanomaterials could change that.

More advance warning could help doctors save more lives.

In conventional test strips, solid gold nanoparticles are often used as labels, where they are connected with antibodies and specifically generate color signal due to an optical phenomenon called localized surface plasmon resonance. Under Xia’s technique, metallic nanomaterials can be crafted with hollow interiors. Compared to the solid counterparts, these hollow nanostructures possess much stronger LSPR activities and thus offer more intense color signal. Therefore, when the hollow nanomaterials are used as labels in test strips they can induce sensitive color change, enabling the strips to detect biomarkers at lower concentrations.

“Test-strip technology gets upgraded by simply replacing solid gold nanoparticles with the unique hollow nanoparticles, while all other components of a test strip are kept unchanged,” says Xia. “Just like the pregnancy test, the new test strip can be performed by non-skilled persons, and the results can be determined with the naked eye without the need of any equipment. These features make the strip extremely suitable for use in challenging locations such as remote villages.”

The UCF study focused on prostate-specific antigen, a biomarker for prostate cancer. The new test strip based on hollow nanomaterials was able to detect PSA as low as 0.1 nanogram per milliliter (ng/mL), which is sufficiently sensitive for clinical diagnostics of prostate cancer. The published study includes electron microscope images of the metallic hollow nanomaterials.

“I hope that by providing a general and versatile platform to engineer functional hollow nanomaterials with desired properties, new research with the potential for other applications beyond biosensing can be launched,” Xia says.

Collaborators on the study include Zhuangqiang Gao, Zheng Xi, Haihang Ye, Zhiyuan Wei and Shikuan Shao from UCF’s chemistry department; Qingxiao Wang and Moon J. Kim from the University of Texas at Dallas, and Dianyong Tang from Chongqing University of Arts and Sciences in China.


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Test strips for cancer detection get upgraded with nanoparticle bling


More information: Zhuangqiang Gao et al. Template Regeneration in Galvanic Replacement: A Route to Highly Diverse Hollow Nanostructures, ACS Nano (2020). DOI: 10.1021/acsnano.9b07781

Journal information: ACS Nano

Active Ingredients-Coated Nanoparticles Could Destroy Cancer Cells


Coated Nano Particles 1 image3D architecture of the cell with different organelles: mitochondria (green), lysosomes (purple), multivesicular bodies (red), endoplasmic reticulum (cream). Image Credit: © Burcu Kepsutlu/HZB.

Nanoparticles have the ability to make their way easily into cells. For the first time, high-resolution 3D microscopy images from BESSY II offer new insights about their distribution and function.

Nanoparticles easily penetrate cells. How they are distributed there and what they do is shown for the first time by high-resolution 3D microscopy images on BESSY II. For example, certain nanoparticles accumulate preferentially in certain organelles of the cell. This can increase the energy turnover in the cell. “The cell looks like a marathon, obviously it takes energy to absorb such nanoparticles,” says lead author James McNally.

Today, nanoparticles are not only in cosmetic products, but everywhere, in the air, in water, in the soil and in food. Because they are so tiny, they easily penetrate cells in our body. This is also of interest for medical applications: Nanoparticles coated with active ingredients could be specifically introduced into cells, for example to destroy cancer cells. However, a lot has hardly been researched: for example, how nanoparticles are distributed in the cells, what they do there and how this effect depends on their size and coating.

Overview of the entire cell

A study at BESSY II has now brought new insights, where Prof. Gerd Schneider’s team can carry out X-ray microscopy images with soft, intensive X-rays. A group around the HZB biophysicist Dr. James McNally has used X-ray microscopy to examine cells with differently coated nanoparticles. The nanoparticles were exactly the same size, but coated with different active ingredients. “X-ray microscopy offers significantly better resolutions than light microscopy and a much better overview than electron microscopy,” emphasizes Schneider.

coloredorganelles_v2

 

The cell looks like it has just run a marathon, apparently, the cell requires energy to absorb such nanoparticles. – Dr James McNally, Study Lead Author and Biophysicist, Helmholtz-Zentrum Berlin

 

Energy storage is decreasing

“X-ray microscopy allows us to see the cell as a whole, so we were able to observe this peculiarity for the first time,” explains McNally. “We found that the uptake of nanoparticles increases the number of mitochondria and endosomes, while other organelles, namely lipid droplets and multivesicular bodies, decrease,” says Burcu Kepsutlu, who carried out the experiments for her doctorate.

 When we go on a starvation diet or run a marathon, we see similar changes in the cell – namely an increase in mitochondria and a decrease in lipid droplets,” says McNally. “Apparently it takes energy for the cell to absorb the nanoparticles, and it feels like after a marathon.”

Accumulation in organelles

For the first time, they received complete, three-dimensional, high-resolution images of the cells with the organelles contained therein, including lipid droplets, multivesicular bodies, mitochondria and endosomes. Lipid droplets act as energy stores in the cell, while mitochondria metabolize this energy. 

The analysis of the images showed: The nanoparticles accumulate preferentially in cell organelles and then change the number of certain organelles in favor of other organelles. These changes were almost independent of the respective coating of the nanoparticles. This suggests that different coatings could have similar effects.  Further studies with other types of nanoparticles and in particular other cell types must show whether this effect can be generalized.

lipiddropletspressrelease

3D Image of the Cell and its Organelles

X-ray microscopy offers significantly better resolution than light microscopy, and a much better overview than electron microscopy. – Gerd Schneider, Professor, Helmholtz-Zentrum Berlin

The researchers acquired, for the first time, comprehensive, 3D, high-resolution images of the cells treated with the nanoparticles, where the organelles—including mitochondria, lipid droplets, endosomes, and multivesicular bodies—were contained within. Lipid droplets act as energy stores in the cell, while mitochondria metabolize this energy.

Accumulation of Nanoparticles

Investigation of the images revealed that the nanoparticles tend to build up preferentially within a subset of the cell organelles. Moreover, the nanoparticles alter the number of particular organelles at the cost of other organelles.

The variations in the numbers of organelles were identical irrespective of the nanoparticle coating. This shows that various different types of nanoparticle coatings may produce a similar effect. Further research with other cell types and with other nanoparticle coatings is necessary to assess how general this effect is.

Number of Lipid Droplets Decreases

X-ray microscopy allows us to see the cell as a whole, so we were able to observe this behavior for the first time,” McNally explained.

We found that the absorption of such nanoparticles increases the number of mitochondria and endosomes, while other organelles, namely lipid droplets and multivesicular bodies, decrease. – Burcu Kepsutlu, Researcher, Helmholtz-Zentrum Berlin

Kepsutlu performed the experiments for her doctorate.

 

ACS Nano (2020): Cells Subject Major Changes in the Quantity of Cytoplasmic Organelles after Uptake of Gold Nanoparticles with Biologically Relevant Surface Coatings, Burcu Kepsutlu, Virginia Wycisk, Katharina Achazi, Sergey Kapishnikov, Ana Joaquina Pérez-Berná, Peter Guttmann, Antje Cossmer , Eva Pereiro, Helge Ewers, Matthias Ballauff, Gerd Schneider, James G. McNally

DOI: 10.1021 / acsnano.9b09264

 

 

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


Waterloo QC Cancer 5c7d5fb4c0cfd

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.