Tag: nanomedicine

Categories : Medical Research & TechnologyTags :

Ancient Medicinal Minerals Inspire New Tissue Repair Technology

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Photo by MJ RAHNAMA

For centuries, civilizations have used naturally occurring, inorganic materials for their perceived healing properties. Egyptians thought green copper ore helped eye inflammation, the Chinese used cinnabar for heartburn, and Native Americans used clay to reduce soreness and inflammation.

Today, researchers at Texas A&M University are still discovering ways that inorganic materials can be used for healing.

In two recently published articles, Dr Akhilesh Gaharwar, a Tim and Amy Leach Endowed Professor in the Department of Biomedical Engineering, and Dr Irtisha Singh, assistant professor in the Department of Cell Biology and Genetics, uncovered new ways that inorganic materials can aid tissue repair and regeneration.

The first article, published in Acta Biomaterialia, explains that cellular pathways for bone and cartilage formation can be activated in stem cells using inorganic ions. The second article, published in Advanced Science, explores the usage of mineral-based nanomaterials, specifically 2D nanosilicates, to aid musculoskeletal regeneration.

“These investigations apply cutting-edge, high-throughput molecular methods to clarify how inorganic biomaterials affect stem cell behavior and tissue regenerative processes,” Singh said.

The ability to induce natural bone formation holds promise for improvements in treatment outcomes, patient recovery times and the reduced need for invasive procedures and long-term medication.

“Enhancing bone density and formation in patients with osteoporosis, for example, can help mitigate the risks of fractures, lead to stronger bones, improve quality of life and reduce healthcare costs,” Gaharwar said. “These insights open up exciting prospects for developing next-generation biomaterials that could provide a more natural and sustainable approach to healing.”

Gaharwar said the newfound approach differs from current regeneration methods that rely on organic or biologically derived molecules and provides tailored solutions for complex medical issues.

“One of the most significant findings from our research is the ability of these nanosilicates to stabilise stem cells in a state conducive to skeletal tissue regeneration,” he said. “This is crucial for promoting bone growth in a controlled and sustained manner, which is a major challenge in current regenerative therapies.”

Gaharwar recently received a grant for his work in using inorganic biomaterials in conjunction with 3D bioprinting techniques to design custom bone implants for reconstructive injuries.

“In reconstructive surgery, particularly for craniofacial defects, induced bone growth is crucial for restoring both function and appearance, vital for essential functions like chewing, breathing and speaking,” he said. “Inducing bone formation has several critical applications in orthopaedics and dentistry.”

“This approach not only bridges ancient practices with modern scientific methods but also minimises the use of protein therapeutics, which carry risks of inducing abnormal tissue growth and cancerous formations,” Gaharwar said. “Collectively, these findings elucidate the potential of inorganic biomaterials to act as powerful mediators in tissue engineering and regenerative strategies, marking a significant step forward in the field.”

Source: Texas A&M University

Categories : CancerTags :

An Electrifying Solution to Destroy Glioblastomas

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Photo by Zoltan Tasi on Unsplash

In Nature Nanotechnology, researchers report a new way to target and kill cancer cells in glioblastomas, hard-to-treat brain tumours, using electrically charged molecules to trigger self-destruction, that could be developed into a spray treatment used during surgery.

Researchers from the University of Nottingham found a new way to harness the extraordinary capabilities of bio-nanoantennae: gold nanoparticles intricately coated with specialised redox active molecules to induce apoptosis, in cancer cells on electrical stimulation.

The research focuses on patient-derived glioblastoma cells, an elusive and formidable form of brain cancer that has long evaded effective treatment. The five-year survival rate for glioblastoma is only 6.8% and the estimated average length of survival is about only 8 months from diagnosis.

The bio-nanoantennae were able to specifically target glioblastoma cells, leaving healthy cells unscathed. This unprecedented level of precision opens up new possibilities for developing treatment for glioblastoma during surgical resection of the tumour, when the bio-nanoantennae would be sprayed or injected.

The researchers, which included experts from the Schools of Engineering, Physics and Medicine have now established what is thought to be the first ‘quantum therapeutic’, which taps into the potential of quantum signalling to combat cancer.

Dr Frankie Rawson led the research and explains: “The team showed that cancer cells succumb to the intricate dance of electrons, orchestrated by the enchanting world of quantum biology. With the advent of bio-nanoantennae, this vision of real-world quantum therapies edge closer to reality. By precisely modulating quantum biological electron tunnelling, these ingenious nanoparticles create a symphony of electrical signals that trigger the cancer cells’ natural self-destruction mechanism.”

The team has now secured MRC impact acceleratory funding, have filed patent, to begin translating the technology to this eventual clinical application. Further rigorous research and validation are essential to ensure the safety and effectiveness of bio-nanoantennae for human use.

Dr Ruman Rahman from the School of Medicine and co-author of the study, adds: “Treating glioblastoma tumours has long presented challenges for clinicians and prognosis for patients is still poor, which is why any research showing the promise of a new effective treatment is hugely exciting. This research has shown the possibilities presented by quantum therapeutics as a new technology to communicate with biology. The fusion of quantum bioelectronics and medicine brings us one step closer to a new treatment paradigm for disease.”

Source: University of Nottingham

Categories : GastrointestinalTags :

Nanomedicine Stimulates Anti-inflammatory Effects to Ease IBD

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Chronic inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, is on the rise worldwide, and current medications have problematic side effects. In the journal Angewandte Chemie, researchers report a new method of treatment, based on nanoparticles which trigger anti-inflammatory effects in the diseased sites in the intestine.

Stomach cramps and severe diarrhoea, often accompanied by significant weight loss, are some of the symptoms repeatedly suffered by patients with IBD, often for weeks at a time. The causes of this condition remain unclear but seem to involve a malfunction of the immune system. A cure is not yet in sight. Current treatments aim to reduce symptoms with anti-inflammatory medications, such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators. Their long-term use is not recommended because of their severe side effects, such as a high risk of infection resulting from immunosuppression. A team led by Hee-Seung Lee and Sangyong Jon at the Korea Advanced Institute of Science and Technology (KAIST) has now developed an innovative approach for a medication that can be taken orally and targets the inflamed sites in the gastrointestinal tract, minimizing systemic effects.

The starting point of their approach was the glycocalyx, a carbohydrate-rich layer that coats the cells on the surface of the intestine. Beneficial gut bacteria, which have their own matching glycocalyx, attach to this coating. With diseases from the IBD family, the glycocalyx carbohydrate patterns of inflamed intestinal regions are so altered that pathogenic bacteria can attach and enter the mucous membrane.

The team developed nanoparticles that mimic the glycocalyx pattern. Starting with the five sugar monomers most commonly found in nature, they produced a collection (“substance library”) of different polymer chains that have one, two, three, four, or five of these sugars in random order and composition as side chains. These polymer chains aggregate into nanoparticles. They also attached bilirubin molecules. Bilirubin is a bile pigment that is an antioxidant naturally produced by the body and it has an anti-inflammatory effect.

When administered orally to mice with IBD, some versions of these nanoparticles reduced symptoms significantly better than the drug 5-ASA. Nanoparticles with mannose and N-acetylglucosamine were the most effective. These two sugars increase uptake of the nanoparticles by activated macrophages in the inflamed intestine, and bilirubin very efficiently inhibits the inflammatory activity of these immune cells. The concentration of certain inflammatory cytokines is significantly reduced, the production of anti-inflammatory factors is stimulated, and oxidative stress is reduced. The immunosuppressive effect is limited to the inflamed areas of the intestine, minimising unfavourable systemic side effects.

Source: Wiley

Categories : Medical Research & TechnologyTags :

New Coating Makes the Nanomedicine Go Down

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Upon injection into the blood, nanomedicines (blue spheres) are immediately attacked by proteins of the immune system called complement proteins (orange). Complement proteins cause rapid destruction of the nanomedicine, and also induce an anaphylaxis-like reaction. By attaching complement-degrading proteins (yellow ninjas made of protein) to the surface of nanomedicines, Penn researchers have largely solved this problem, potentially allowing more diseases to be safely treated by nanomedicine. Credit: University of Pennsylvania

In nanomedicine, immune reactions against the nanoparticles that contain the medicine or vaccine, reducing its effectiveness. Researchers have now come up with a new method to prevent the body from treating nanomedicines like foreign invaders, by covering those nanoparticles with a coating to suppress the immune response.

As soon as they are injected into the bloodstream, unmodified nanoparticles are swarmed by complement proteins, triggering an inflammatory response and preventing the nanoparticles from reaching their treatment targets. Penn Medicine researchers, whose findings are published in Advanced Materials, have devised a coating for nanoparticles that suppresses complement activation.

Nanoparticles are tiny capsules, typically made from proteins or fat-related molecules, that contain certain types of treatment or vaccine. The best-known examples of nanoparticle-delivered medicines are mRNA COVID vaccines.

“It turned out to be one of those technologies that just works right away and better than anticipated,” said study co-senior author Jacob Brenner, MD, PhD.

RNA- or DNA-based therapies generally need delivery systems to get them through the bloodstream into target organs. Harmless viruses often have been used as carriers or “vectors” of these therapies, but nanoparticles are increasingly considered safer alternatives. Nanoparticles also can be tagged with antibodies or other molecules that make them hone in precisely on targeted tissues.

The complement attack problem has been a serious impediment to nanomedicine. Circulating complement proteins treat nanoparticles as if they were bacteria, immediately coating nanoparticle surfaces and summoning macrophages to engulf them. Researchers have attempted to reduce the problem by pre-coating nanoparticles with camouflaging molecules, such as forming a watery, protective shell around nanoparticles using polyethylene glycol (PEG).

But nanoparticles camouflaged with substances like PEG still draw at least some complement attack. In general, nanoparticle-based medicines that move through the bloodstream (mRNA COVID vaccines are injected into muscle, not the bloodstream) have had a very low efficiency in getting to their target organs, usually under 1%.

In the study, the researchers came up with a new approach to protect nanoparticles, based on natural complement-inhibitor proteins that circulate in the blood, attaching to human cells to help protect them from complement attack.

In vitro tests using standard PEG-protected nanoparticles with one of these complement inhibitors, called Factor I, provided dramatically better protection from complement attack. In mice, the same strategy prolonged the half-life of standard nanoparticles in the bloodstream, allowing a much larger fraction of them to reach their targets.

“Many bacteria also coat themselves with these factors to protect against complement attack, so we decided to borrow that strategy for nanoparticles,” said co-senior author Jacob Myerson, PhD, a senior research scientist in the Department of Systems Pharmacology and Translational Therapeutics at Penn.

In a set of experiments in mouse models of severe inflammatory illness, the researchers also showed that attaching Factor I to nanoparticles prevents the hyper-allergic reaction that otherwise could be fatal.

Further testing will be needed before nanomedicines incorporating Factor I can be used in people, but in principle, the researchers said, attaching the complement-suppressing protein could make nanoparticles safer and more efficient as therapeutic delivery vehicles so that they could be used even in severely ill patients.

The researchers now plan other protective strategies for medical devices, such as catheters, stents and dialysis tubing, which are similarly susceptible to complement attack. They also plan to investigate other protective proteins.

“We’re recognising now that there’s a whole world of proteins that we can put on the surface of nanoparticles to defend them from immune attack,” Dr Brenner said.

Source: University of Pennsylvania School of Medicine

Categories : CancerTags :

Nanoparticles Deliver Chemotherapy to Cancer Cell’s Doorsteps

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Fanciful depiction of nanoparticles. Photo by Landon Arnold on Unsplash

New research has developed a nanoparticle system that can deliver large, unwieldy protein-based chemotherapy drugs right to the doorsteps of cancer cells.

Some cancer treatments make use of antibodies’ ability to recognise specific cancer cells in order to target those cells with small active agents, but have not been able to deliver larger protein-based drugs.

Research published in the journal Angewandte Chemie shows how, using a new protein transport system, proteins can arrive at their target intact, protected from destructive proteases by polymer brushes.

Two problems keep coming up when scientists try to develop new anticancer drugs. Firstly, an active agent needs to be able to kill the body’s cells at the root of the cancer, and secondly it should be active in target cancer cells rather than in healthy cells. To this end, some medical researchers are  trying to implement a cargo package as a method of delivery. The active agent stays protected and packaged until it reaches the target location, while antibodies that only attach to cancer cells help with “finding the right address”. 

These antibodies recognise specific receptor structures on the outer membrane of cancer cells, attaching to these structures with the cell absorbing the active agent. However, this strategy is unsuccessful when the active agents are large proteins. 

These large proteins are usually water soluble, and unable to penetrate the cell membrane. The body’s own protease enzymes throw in another complication, because they break down the protein cargoes before they can reach their target location.

Sankaran Thayumanavan and colleagues at the University of Massachusetts in Amherst, USA, have now developed a protected nanosized cargo package, which meets both requirements of targeted delivery and keeping the cargo intact. For the container, they use miniscule beads made of silicon dioxide with a diameter of just 200 nanometres. The surface of these beads is coated with brush-like polymer strands made of polyethylene glycol (PEG) that can be doubly functionalised, giving tiny “brush beads”. This is termed a protein-antibody conjugate (PAC).

With simple click chemistry, the researchers attach the desired active-agent protein and antibodies to the polymer bristles. The finished bead-shaped packages have antibodies on the outermost layer, with the proteins safely concealed in the forest of polymer strands.

Besides the ability to transport water-soluble proteins, this PAC also possessed another advantage: a possible high protein-antibody ratio. The researchers said that, at least in theory, over 10 000 proteins could be transported per (expensive) antibody using the researchers’ PACs, compared to the maximum of four active agents per antibody in previous antibody-drug combinations.

The team tested their system on various cell cultures with different antibodies and test proteins. The test was a success; the PACs delivered their deadly cargoes to their cellular targets as planned.
The team is now going to figure out if and how the packages can be shielded from macrophages. They are optimistic about this because the PEG functionalities and the surface antibodies are designed for a quick delivery while minimising clearance by macrophages.

Source: News-Medical.Net

Journal information: Liu, B., et al. (2021) Protein–Antibody Conjugates (PACs): A Plug‐and‐Play Strategy for Covalent Conjugation and Targeted Intracellular Delivery of Pristine Proteins. Angewandte Chemie International Edition. doi.org/10.1002/anie.202103106.

Categories : CancerTags :

Wrapping up Tumours With Micromesh Nets

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An innovative new nanomedicine has been developed that wraps up tumours in a micromesh net, conforming to the surface of tumor masses and efficiently delivering drugs.

The scientists at the IIT (Istituto Italiano di Tecnologia (Italian Institute of Technology) who developed the mesh described it in the journal Nature Nanotechnology.

Brain tumors are rare but they are some of the most aggressive and difficult to treat. In particular, glioblastoma multiforme (GBM), which is a grade 4 glioblastoma has the most severe prognosis: the average survival is just over 12 months and only 5% of the patients survive beyond 5 years.

GBM typically affects men and women between 45 and 75 years of age. Furthermore, unlike other malignancies, there has been no significant diagnostic and therapeutic improvements for this malignancy over the past 30 years. In fact, both the incidence of new cases and the number of deaths has remained practically unchanged. The only therapeutic strategy currently used is based on surgery, which consists of removing a part of the tumor mass and reducing intracranial pressure, followed by radiotherapy and/or chemotherapy.

The biomedical system developed by IIT and its collaborators can play a very important role in the fight against the disease, representing a possible effective alternative to the few pharmacological treatments used to date.

The microMESH is a micrometric-scale polymeric net, made from biodegradable materials and wraps around the tumour mass, enclosing it. In fact, the micrometric thick polymeric fibers are very flexible and are arranged to form regular openings, which are also on the same scale as cancer cells. This unique feature allows the microMESH to achieve a closer interaction with the tumor mass, increasing the therapeutic efficacy.

Its structure consists of two separate compartments in which different drugs can be loaded which are released towards the tumor mass in an independent, precise, and prolonged fashion. Combining different therapies: chemotherapy, nanomedicine, and immunotherapy enables the microMESH to ‘attack’ glioblastoma.

This work has been carried out by a team led by Prof Paolo Decuzzi, head of the IIT Laboratory of Nanotechnology for Precision Medicine, in collaboration with the Neural Stem Cell Biology Laboratory of Dr Rossella Galli at the San Raffaele Hospital in Milan and a team led by Prof Gerald Grant at the Lucile Packard Children’s Hospital of Stanford University.

The group will continue to develop the microMESH by integrating different types of drugs and therapies to tackle other types of tumors. In the short term, their major objective will be to validate the technology on glioblastoma patients.

Source: News-Medical.Net

Journal information: Mascolo, D. D., et al. (2021) Conformable hierarchically engineered polymeric micromeshes enabling combinatorial therapies in brain tumours. Nature Nanotechnology. doi.org/10.1038/s41565-021-00879-3.