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.

Nanotechnology for disease diagnosis and treatment earns Florida Poly professor international award

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Florida Polytechnic University professor Dr. Ajeet Kaushik received the 2019 USERN Prize in biological sciences, an international award recognizing his work in the field of nanomaterials for the detection and treatment of diseases.

Florida Polytechnic University professor Dr. Ajeet Kaushik is determined to make detecting and treating diseases easy, accessible, and precise through the use of nanomaterials for biosensing and medicine.

His extensive work and resolute desire to improve the delivery of healthcare has earned Kaushik the prestigious Universal Scientific Education Research Network (USERN) Prize. He was named a laureate in the field of biological sciences during the group’s fourth annual congress on Nov. 8 in Budapest, Hungary.

USERN, a non-governmental, non-profit organization and network dedicated to non-military scientific advances, is committed to exploring science beyond international borders.

“I was speechless for a while,” said Kaushik, who is an assistant professor of chemistry at Florida Polytechnic University.

Kaushik did not attend the awards ceremony in person but did submit a video to be played at the event. He was among hundreds vying for the prize and one of five people who were recognized in different areas of study.

His submitted project, Nano-Bio-Technology for Personalized Health Care, focuses on using nanomaterials to create biosensors that will detect the markers of a disease at very low levels.

“Biosensing is not a new concept, but now we are making devices that are smarter and more capable,” Kaushik said.

He cited the recent zika virus epidemic that affected pregnant women and their fetuses, leading to significant health complications upon birth.

“There was a demand to have a system that could detect the virus protein at a very low level, but there was no device. There was no diagnostic system,” he said.

Kaushik worked on the development of a smart zika sensor that could detect the disease at these low levels.

“The kind of systems I’m focusing on can be customized in a way that we carry like a cell phone and do the tests wherever we need to do them,” he said.

In addition to using nanotechnology for the detection of diseases like zika, his research on nanoparticles is advancing efforts to precisely deliver medicine to a specific part of the body without affecting surrounding tissue or other parts of the body.

“The drugs we use now do not go only where they need to go, or sometimes they have side effects. We are treating one disease but creating other symptoms,” Kaushik said. “I’m exploring nanotechnology that can carry a drug, selectively go to a place, and release the drug so we avoid using excessive drugs.”

This nanomedicine could be used to precisely target brain tumors or other difficult-to-treat conditions.

He has published papers in scientific journals about this work and also holds multiple patents.

“My whole approach is using smart material science for better health for everybody, which is accessible to everybody everywhere,” Kaushik said.

In addition to his USERN prize, Kaushik was named a USERN junior ambassador for 2020 and will work to advance the organization’s mission in the United States.

For the most recent university news, visit Florida Poly News.

About Florida Polytechnic University: Florida Polytechnic University is accredited by the Southern Association of Colleges and Schools Commission on Colleges and is a member of the State University System of Florida. It is the only state university dedicated exclusively to STEM and offers ABET accredited degrees. Florida Poly is a powerful economic engine within the state of Florida, blending applied research with industry partnerships to give students an academically rigorous education with real-world relevance. Connect with Florida Poly.

Unique Rice platform helps bioscientists learn how ectoderm cells begin to differentiate


During embryonic development, the entire nervous system, the skin and the sensory organs emerge from a single sheet of cells known as the ectoderm. While there have been extensive studies of how this sheet forms all these derivatives, it hasn’t been possible to study the process in humans – until now.

Rice bioscientist Aryeh Warmflash, graduate student George Britton and their colleagues have created a system in which all of the major cell types of ectoderm are formed in a culture dish in a pattern similar to that seen in embryos.This technique, based on controlling the geometry of stem cell colonies with microscale patterns, has helped them make the most comprehensive analysis yet of signaling pathways that drive patterning of human ectoderm.

“There are very few possible signals the embryo uses to generate the wide variety of cell types that arise,” Britton said. “We want to understand the timing of these signals and how the cells interpret them in time to generate this variety.”

It revealed that the balance between two signaling pathways, BMP and Wnt, are both critical, and even a bit adaptable as they orchestrate patterning in the ectoderm. The logic they employ ultimately drives ectodermal cells to their fates, but the research showed they can take more than one road to get there.

Britton said the micro-patterned plates and a better understanding of how the signaling pathways work let them manipulate stem cell colonies to form unusual patterns at the start, but ultimately they always seemed to converge at the same place. “We found different trajectories of the signals that arrived at the same pattern,” he said. That suggested the system by which stem cells become neurons, neural crest cells, neurogenic placodes and epidermis cells is pretty robust.

“A lot of people are interested in the transcription factor network that directs neural crest emergence, so this is a powerful system to dissect the signals that contribute to that logic,” Britton said. “That was one thing we feel we contributed to the field.

“There’s also the idea that cells that have the ability to interpret relative levels of BMP and Wnt to incorporate the appropriate fate decision,” he said. “In the embryo, cells are moving around quite a bit in a space where signals and the ligands they’re exposed to are also moving around. It might be that cells are reading the relative levels to determine a certain fate.”

The researchers observed that the relative activity of BMP and Wnt signaling determines cells’ decisions to become either neural crest or placodal cells, while BMP alone initiates and controls the size of the surface ectoderm, all within about the first four days.

“Four days is about right in the sense that cells are starting to make decisions: ‘I’m going to be a placodal cell, I’m going to be a neural crest cell, I’m going to be neural fate and I’m going to an epidermal fate,” Britton said.
Unique Rice platform helps bioscientists learn how ectoderm cells begin to differentiate
“We see that approximately a day or two after BMP treatment. But it’s hard to put a finger on whether these are the final patterns,” he said. “We’d have to do a more careful observation to make sure those placodal cells don’t change to neural crest cells, or vice versa. That will give us information on how these lineages and fates settle into a final pattern, maybe by day 6 or 7.”

He said future studies will further refine their understanding of how signaling patterns work, as well as how the development of all the germ layers collaborate.

“Until now, studies of human stem cells differentiating to ectodermal fates were mostly about how to get all the cells in your culture dish to become a particular cell type; for example, how to make a dish full of neurons,” Warmflash said. “We are interested in a different question: How do cells interact with each other to make patterns of different cell fates? The system we developed does this outside the embryo and is allowing us to begin to tackle this question.”

Rice University

Nanomesh Drug Delivery provides Hope against Global Antibiotic Resistance


The fight against global antibiotic resistance has taken a major step forward with scientists discovering a concept for fabricating nanomeshes as an effective drug delivery system for antibiotics.

Health experts are increasingly concerned about the rise in medication resistant bacteria.

Flinders University researchers and collaborators in Japan have produced a nanomesh that is capable of delivering drug treatments.

In studying the effectiveness of the nanomesh, two antibiotics, Colistin and Vancomycin, were added together with gold nanoparticles to the mesh, before they were tested over a 14 day period by PHD student Melanie Fuller.

Flinders Institute for Nanoscience and Technology Associate Professor Ingo Koeper says 20cm by 15cm pieces of mesh were produced which contain fibres 200 nm in diameter. These meshes are produced using a process called electrospinning with parameters being optimised to ensure the mesh material was consistent.

“In order to deliver the antibiotics to a specific area, the antibiotics were embedded into the mesh produced using a technique called electrospinning, which has gained considerable interest in the biomedical community as it offers promise in many applications including wound management, drug delivery and antibiotic coatings,” says Assoc Prof. Koeper

“A high voltage is then applied between the needle connected to the syringe, and the collector plate which causes the polymer solution to form a cone as it leaves the syringe, at which point the electrostatic forces release a jet of liquid.”

“Small charged nanoparticles altered the release of the antibiotics from the nanomesh. The addition of gold nanoparticles likely neutralised charge, causing the antibiotic to migrate toward the centre of the fibre, prolonging its release.”

The results also suggest dosages could be reduced when compared to traditional drugs which can also diminish potential side effects and complications.

“Although the dosage is reduced compared to an oral dosage, the concentration of antibiotics delivered to the infection site can still be higher, ensuring the bacteria cannot survive which will reduce instances of resistance.”

“This research, as a proof of concept, suggests an opportunity for fabricating nanomeshes which contain gold nanoparticles as a drug treatment for antibiotics.”

Working with Dr. Harriet Whiley, a Flinders environmental health scientists, the researchers studied how the release of the drugs affected the growth of E. Coli. The in vitro study confirmed Colistin with negatively charged gold nanoparticles produced the most efficient nanomesh, significantly affecting bacterial growth.

“Further investigation is needed to determine if other small charged particles affect the release of drugs and how it affects the release over time. As it is a pharmaceutical application, the stability of the mesh under different storage conditions as well as the toxicological properties also need to be evaluated.”






DNA ‘Origami’ takes Flight in Emerging Field of Nano Machines – “(a) … tool may eventually be used to fine tune immunotherapies for individual cancer patients”

DNA mechanotechnology expands the opportunities for research involving biomedicine and materials sciences, says Khalid Salaita, right, professor of chemistry at Emory University and co-author of the article, along with Aaron Blanchard, left, a graduate student in the Salaita Lab. Credit: Emory University

Just as the steam engine set the stage for the Industrial Revolution, and micro transistors sparked the digital age, nanoscale devices made from DNA are opening up a new era in bio-medical research and materials science.

The journal Science describes the emerging uses of DNA  in a “Perspective” article by Khalid Salaita, a professor of chemistry at Emory University, and Aaron Blanchard, a graduate student in the Wallace H. Coulter Department of Biomedical Engineering, a joint program of Georgia Institute of Technology and Emory.

The article heralds a new field, which Blanchard dubbed “DNA mechanotechnology,” to engineer DNA machines that generate, transmit and sense  at the nanoscale.

“For a long time,” Salaita says, “scientists have been good at making micro devices, hundreds of times smaller than the width of a human hair. It’s been more challenging to make functional nano devices, thousands of times smaller than that. But using DNA as the component parts is making it possible to build extremely elaborate nano devices because the DNA parts self-assemble.”

DNA, or deoxyribonucleic acid, stores and transmits genetic information as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C) and thymine (T). The DNA bases have a natural affinity to pair up with each other—A with T and C with G. Synthetic strands of DNA can be combined with natural DNA strands from bacteriophages. By moving around the sequence of letters on the strands, researchers can get the DNA strands to bind together in ways that create different shapes. The stiffness of DNA strands can also easily be adjusted, so they remain straight as a piece of dry spaghetti or bend and coil like boiled spaghetti.

The idea of using DNA as a construction material goes back to the 1980s, when biochemist Nadrian Seeman pioneered DNA nanotechnology. This field uses strands DNA to make functional devices at the nanoscale. The ability to make these precise, three-dimensional structures began as a novelty, nicknamed DNA origami, resulting in objects such as a microscopic map of the world and, more recently, the tiniest-ever game of tic-tac-toe, played on a DNA board.

Work on novelty objects continues to provide new insights into the mechanical properties of DNA. These insights are driving the ability to make DNA machines that generate, transmit and sense mechanical forces.

“If you put together these three main components of mechanical devices, you begin to get hammers and cogs and wheels and you can start building nano machines,” Salaita says. “DNA mechanotechnology expands the opportunities for research involving biomedicine and materials science. It’s like discovering a new continent and opening up fresh territory to explore.”

Potential uses for such devices include drug delivery devices in the form of nano capsules that open up when they reach a target site, nano computers and nano robots working on nanoscale assembly lines.

The use of DNA self-assembly by the genomics industry, for biomedical research and diagnostics, is further propelling DNA mechanotechnology, making DNA synthesis inexpensive and readily available. “Potentially anyone can dream up a nano-machine design and make it a reality,” Salaita says.

He gives the example of creating a pair of nano scissors. “You know that you need two rigid rods and that they need to be linked by a pivot mechanism,” he says. “By tinkering with some open-source software, you can create this design and then go onto a computer and place an order to custom synthesize your design. You’ll receive your order in a tube. You simply put the tube contents into a solution, let your device self-assemble, and then use a microscope to see if it works the way you thought that it would.”

Salaita’s lab is one of only about 100 around the world working at the forefront of DNA mechanotechnology. He and Blanchard developed the world’s strongest synthetic DNA-based motor, which was recently reported in Nano Letters.

A key focus of Salaita’s research is mapping and measuring how cells push and pull to learn more about the mechanical forces involved in the human immune system.

Salaita developed the first DNA force gauges for cells, providing the first detailed view of the mechanical forces that one molecule applies to another molecule across the entire surface of a living cell. Mapping such forces may help to diagnose and treat diseases related to cellular mechanics. Cancer cells, for instance, move differently from normal cells, and it is unclear whether that difference is a cause or an effect of the disease.

In 2016, Salaita used these DNA force gauges to provide the first direct evidence for the mechanical forces of T cells, the security guards of the immune system. His lab showed how T cells use a kind of mechanical “handshake” or tug to test whether a cell they encounter is a friend or foe. These mechanical tugs are central to a T cell’s decision for whether to mount an immune response.

“Your blood contains millions of different types of T cells, and each T cell is evolved to detect a certain pathogen or foreign agent,” Salaita explains. “T cells are constantly sampling cells throughout your body using these mechanical tugs. They bind and pull on proteins on a cell’s surface and, if the bond is strong, that’s a signal that the T cell has found a foreign agent.”

Salaita’s lab built on this discovery in a paper recently published in the Proceedings of the National Academy of Sciences (PNAS). Work led by Emory chemistry graduate student Rong Ma refined the sensitivity of the DNA force gauges. Not only can they detect these mechanical tugs at a force so slight that it is nearly one-billionth the weight of a paperclip, they can also capture evidence of tugs as brief as the blink of an eye.

The research provides an unprecedented look at the mechanical forces involved in the immune system. “We showed that, in addition to being evolved to detect certain foreign agents, T cells will also apply very brief mechanical tugs to foreign agents that are a near match,” Salaita says. “The frequency and duration of the tug depends on how closely the foreign agent is matched to the T cell receptor.”

The result provides a tool to predict how strong of an immune response a T cell will mount. “We hope this tool may eventually be used to fine tune immunotherapies for individual cancer patients,” Salaita says. “It could potentially help engineer T  to go after particular .”

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.”

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

Researchers Develop Nanoparticle-Based Vaccine for Skin Cancer


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


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

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

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

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

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

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

A New Approach

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

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

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

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

Successful Prevention and Treatment

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

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

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

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


Tiny capsules offer alternative to viral delivery of gene therapy

A graphic description of the nanocapsule delivery system. Credit: UW-Madison

New tools for editing genetic code offer hope for new treatments for inherited diseases, some cancers, and even stubborn viral infections. But the typical method for delivering gene therapies to specific tissues in the body can be complicated and may cause troubling side effects.

Researchers at the University of Wisconsin-Madison have addressed many of those problems by packing a gene-editing payload into a tiny customizable, synthetic . They described the  and its cargo today (Sept. 9, 2019) in the journal Nature Nanotechnology.

“In order to edit a gene in a cell, the editing tool needs to be delivered inside the cell safely and efficiently,” says Shaoqin “Sarah” Gong, a professor of biomedical engineering and investigator at the Wisconsin Institute for Discovery at UW-Madison. Her lab specializes in designing and building nanoscale delivery systems for targeted therapy.

“Editing the wrong tissue in the body after injecting gene therapies is of grave concern,” says Krishanu Saha, also a UW-Madison biomedical engineering professor and steering committee co-chair for a nationwide consortium on genome editing with $190 million in support from the National Institutes of Health. “If  are inadvertently edited, then the patient would pass on the gene edits to their children and every subsequent generation.”

Most genome editing is done with , according to Gong. Viruses have billions of years of experience invading cells and co-opting the cell’s own machinery to make new copies of the virus. In gene therapy, viruses can be altered to carry genome-editing machinery rather than their own viral  into cells. The editing machinery can then alter the cell’s DNA to, say, correct a problem in the genetic code that causes or contributes to disease.

“Viral vectors are attractive because they can be very efficient, but they are also associated with a number of safety concerns including undesirable immune responses,” says Gong.

New cell targets can also require laborious alterations of viral vectors, and manufacturing tailored viral vectors can be complicated.

“It is very difficult—if not impossible—to customize many viral vectors for delivery to a specific cell or tissue in the body,” Saha says.

Gong’s lab coated a  payload—namely, a version of the gene-editing tool CRISPR-Cas9 with guide RNA designed in Saha’s lab—with a thin polymer shell, resulting in a capsule about 25 nanometers in diameter. The surface of the nanocapsule can be decorated with functional groups such as peptides which give the nanoparticles the ability to target certain .

The nanocapsule stays intact outside cells—in the bloodstream, for example—only to fall apart inside the target cell when triggered by a molecule called glutathione. The freed payload then moves to the nucleus to edit the cell’s DNA. The nanocapsules are expected to reduce unplanned genetic edits due to their short lifespan inside a cell’s cytoplasm.

This project is a collaboration combining UW-Madison expertise in chemistry, engineering, biology and medicine. Pediatrics and ophthalmology professor Bikash R. Pattnaik and comparative biosciences professor Masatoshi Suzuki and their teams worked to demonstrate gene editing in mouse eyes and skeletal muscles, respectively, using the nanocapsules.

Because the nanocapsules can be freeze-dried, they can be conveniently purified, stored, and transported as a powder, while providing flexibility for dosage control. The researchers, with the Wisconsin Alumni Research Foundation, have a patent pending on the nanoparticles.

“The , superior stability, versatility in surface modification, and high editing efficiency of the nanocapsules make them a promising platform for many types of gene therapies,” says Gong.

The team aims to further optimize the nanocapsules in ongoing research for efficient editing in the brain and the eye.

Explore further

Researchers redefine the footprint of viral vector gene therapy

Light and nanotechnology prevent bacterial infections on medical implants – Reducing Costs and Recurring Surgeries

Image of the surgical implants, covered with gold nanoparticles (pile of meshes on the left) compared to the original surgical meshes previous to the treatment (pile of meshes on the right). Credit: ICFO

Invented approximately 50 years ago, surgical medical meshes have become key elements in the recovery procedures of damaged-tissue surgeries, the most common being hernia repair.

When implanted within the tissue of the patient, the flexible and conformable design of these meshes hold muscles securely and allows quicker recovery than conventional surgical procedures of sewing and stitching.

However, the insertion of a medical implant in a patient’s body carries the risk of bacterial contamination during surgery and subsequent formation of an infectious biofilm over the surface of the surgical .

Such biofilms tend to act like a plastic coating, preventing any sort of antibiotic agent from reaching and attacking the formed on the film in order to stop the infection. Thus, antibiotic therapies, which are time-limited, could fail against super-resistant bacteria and the patient could end up in recurring or never-ending surgeries that could even lead to death.

In fact, according to the European Antimicrobial Resistance Surveillance Network (EARS-Net), in 2015, more than 30,000 deaths in Europe were linked to infections with antibiotic-resistant bacteria.

Physicians have used several approaches to prevent implant contamination during surgery. Post-surgery aseptic protocols have been established and implemented to fight these antibiotic-resistant bacteria, but none have entirely fulfilled the role of solving this issue.

SEM micrographs of the S. aureus biofilm formed on the surgical mesh surface. Credit: ICFO

In a recent study published in Nano Letters and highlighted in Nature Photonics, ICFO researchers Dr. Ignacio de Miguel, Arantxa Albornoz, led by ICREA Prof. at ICFO Romain Quidant, in collaboration with researchers Irene Prieto, Dr. Vanesa Sanz, Dr. Christine Weis and Dr. Pau Turon from the B. Braun and pharmaceutical device company, have devised a novel technique that uses nanotechnology and photonics to dramatically improve the performance of medical meshes for surgical implants.

In collaboration since 2012, the team of researchers at ICFO and B. Braun Surgical, S.A., developed a medical mesh with a particular feature: The surface of the mesh was chemically modified to anchor millions of gold nanoparticles.

Why? Because gold nanoparticles have been proven to convert light into heat highly efficiently at localized regions.

The technique of using gold nanoparticles in light-heat conversion processes had already been tested in cancer treatments in previous studies.

Knowing that more than 20 million hernia repair operations take place every year around the world, the researchers believed this method could reduce the medical costs in recurrent operations while eliminating the expensive and ineffective antibiotic treatments that are currently being employed to tackle this problem.

Schematic view of plasmon-enabled biofilm prevention on surgical meshes. Credit: ICFO

Thus, in their in-vitro experiment and through a thorough process, the team coated the surgical mesh with millions of , uniformly spreading them over the entire structure. They tested the meshes to ensure the long-term stability of the particles, the non-degradation of the material, and the non-detachment or release of nanoparticles into the surrounding environment (flask). They were able to observe a homogenous distribution of the nanoparticles over the structure using a scanning electron microscope.

Once the modified mesh was ready, the team exposed it to S. aureus bacteria for 24 hours until they observed the formation of a biofilm on the surface. Subsequently, they began exposing the mesh to short, intense pulses of near  (800 nm) over 30 seconds to ensure  was reached, before repeating this treatment 20 times with four seconds of rest intervals between each pulse.

They discovered the following: First, they saw that illuminating the mesh at the specific frequency would induce localized surface plasmon resonances in the nanoparticles—a mode that results in the efficient conversion of light into heat, burning the bacteria at the surface.

Second, by using a fluorescence confocal microscope, they observed how much of the bacteria had died or was still alive. They observed that the remaining living biofilm bacteria became planktonic cells, recovering their sensitivity or weakness toward antibiotic therapy and to immune system response. They observed that upon increasing the amount of light delivered to the surface of the mesh, the dead bacteria would lose their adherence and peel off the surface. 

Third, they confirmed that operating at near infrared light ranges was completely compatible with in-vivo settings, meaning that such a technique would most probably not damage the surrounding healthy tissue. Finally, they repeated the treatment and confirmed that the recurrent heating of the mesh had not affected its conversion efficiency capabilities.

ICREA Prof at ICFO Romain Quidant says, “The results of this study have paved the way towards using plasmon nanotechnologies to prevent the formation of bacterial biofilm at the surface of surgical implants. There are still several issues that need to be addressed but it is important to emphasize that such a technique will indeed signify a radical change in operation procedures and further patient post recovery.”

Director of Research and Development of B. Braun Surgical, S.A. Dr. Pau Turon, says, “Our commitment to help healthcare professionals to avoid hospital related infections pushes us to develop new strategies to fight bacteria and biofilms. Additionally, the research team is exploring to extend such technology to other sectors where biofilms must be avoided.”

More information: Ignacio de Miguel et al, Plasmon-Based Biofilm Inhibition on Surgical Implants, Nano Letters(2019).  DOI: 10.1021/acs.nanolett.9b00187

Journal information: Nano Letters , Nature Photonics

Provided by ICFO

Scientists Use Near-Infrared Light and Injected DNA Nanodevice to Guide Stem Cells to a Wound – Accelerating the Healing Process


Researchers can guide stem cells (like those in the illustration above) to an injury by using near-infrared light and an injected DNA nanodevice. (Image credit: Juan Gaertner/

Imagine physicians having a remote control that they could employ to drive a patient’s own cells to a wound to accelerate the healing process.

Such a device is still away from reality, however, scientists have described in the ACS journal Nano Letters of having taken a key initial step: They employed near-infrared light and an injected DNA nanodevice to direct stem cells to a wound, which helped in the regrowth of muscle tissue in mice.

Complex signaling pathways synchronize cellular activities like proliferation, movement, and even death. For instance, when signaling molecules attach to proteins known as receptor tyrosine kinases on a cell’s surface, they stimulate the receptors to pair up and phosphorylate each other. This process can trigger other proteins that eventually result in a cell moving or growing.

Hong-Hui Wang, Zhou Nie, and partners doubted if they could set up a nanodevice to cells that would rewire this system, activating the receptors by near-infrared light rather than signaling molecules. The scientists opted for near-infrared as it can penetrate living tissues, in contrast to visible or ultraviolet light. The group aimed a receptor tyrosine kinase known as MET, which is important for wound healing.

The scientists developed a DNA molecule that can attach to two MET receptors at the same time, binding them together and stimulating them. In order to make the system responsive to light, the researchers linked multiple copies of the DNA sequence to gold nanorods. On irradiating near-infrared light, the nanorods get heated up and release the DNA so that it could trigger the receptors.

The scientists introduced the DNA-bound gold nanorods into mice at the injured area and illuminated a near-infrared light on the mice for a few minutes. After three days, more muscle stem cells had moved to the wound in treated mice when compared to those in untreated mice. The treated mice also exhibited improved signs of muscle regeneration in comparison to control mice.

The researchers acknowledge funding from the National Natural Science Foundation of China, National Science and Technology Major Project, the Young Top-Notch Talent for Ten Thousand Talent Program, the Keypoint Research and Invention Program of Hunan Province, and the National Institutes of Health.