Sopping up proteins with thermosponges

PUBLIC RELEASE DATE:

22-Oct-2014

Contact: Nicole Davis nmdavisphd@gmail.com 617-823-3468 Brigham and Women's Hospital @BrighamWomens

Boston, MA A research team led by Brigham and Women's Hospital (BWH) has developed and tested a novel nanoparticle platform that efficiently delivers clinically important proteins in vivo in initial proof-of-concept tests. Nanoparticles, which are particles measuring nanometers in size, hold promise for a range of applications, including human therapeutics. The key advantage of the new platform, known as a thermosponge nanoparticle, is that it eliminates the need for harsh solvents, which can damage the very molecules the particles are designed to carry.

The study is published online October 21 in Nano Letters.

"A central challenge in applying nanoparticle technology to protein therapeutics is preserving proteins' biological activity, which can be inactivated by the organic solvents used in nanoparticle engineering," said Omid Farokhzad, MD, Director of the BWH Laboratory of Nanomedicine and Biomaterials. "Our research demonstrates that the thermosponge platform, which enables the solvent-free loading of proteins, is a promising approach for the delivery of a variety of proteins, including highly labile proteins such as IL-10."

Protein-based therapeutics form an important class of drugs to treat a range of human diseases. However, significant challenges in their development have generally resulted in very slow development paths. To overcome these challenges, Farokhzad and his colleagues sought to create improved nanoparticle methods for delivering protein therapies.

The new thermosponge nanoparticles (TNPs) they developed are composed of biocompatible and biodegradable polymers. These polymers include a central, spherical core, made of the polymer poly(D,L-lactide), and an outer "thermosponge," made of a polaxomer polymer. The core can be either positively or negatively charged, to allow for the delivery of negatively or positively charged proteins, respectively. Importantly, the thermosponge shell can expand or contract as temperatures change, which permits the solvent-free loading of proteins onto the TNP.

The researchers selected a range of different proteins for loading onto the TNPs, including positively-charged interleukin-10 (IL-10) and erythropoietin, and negatively-charged insulin and human growth hormone. The proteins showed similar patterns of sustained release for four days after loading, indicating that the TNPs are able to effectively deliver a variety of proteins.

Further tests showed that the proteins loaded onto the TNPs retained their bioactivity throughout both loading and release from the TNPs.

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Sopping up proteins with thermosponges

Can a bodys own stem cells help heal a heart?

If you skin your knee, your body makes new skin. If you donate a portion of your liver, whats left will grow back to near-normal size. But if you lose a billion heart cells during a heart attack, only a small fraction of those will be replaced. In the words of Ke Cheng, an associate professor of regenerative medicine at N.C. State, The hearts self-repair potency is very limited.

Cheng has designed a nanomedicine he hopes will give the heart some help. It consists of an engineered nanoparticle that gathers the bodys own self-repair cells and brings them to the injured heart tissue.

In this case, the self-repair cells are adult stem cells. A stem cell is a very rich biological factory, Cheng said. Stem cells can become heart muscle, or they can produce growth factors that are beneficial to the regrowth of heart muscle.

After a heart attack, dying and dead heart cells release chemical signals that alert stem cells circulating in the blood to move to the injured site. But there just arent very many stem cells in the bloodstream, and sometimes they are not sufficiently attracted to the injured tissue.

Matchmakers with hooks

The nanomedicine Cheng designed consists of an iron-based nanoparticle festooned with two different kinds of hooks one kind of hook grabs adult stem cells, and the other kind of hook grabs injured heart tissue. Cheng calls the nanomedicine a matchmaker, because it brings together cells that can make repairs with cells that need repairs.

The hooks are antibodies that seek and grab certain types of cells. Because the antibodies are situated on an iron nanoparticle, they and the stem cells theyve grabbed can be physically directed to the heart using an external magnet. Cheng calls the nanomedicine MagBICE, for magnetic bifunctional cell engager.

The magnet is a first pass to get the iron-based particles and antibodies near the heart. Once there, the antibodies are able to identify and stick to the injured heart tissue, bringing the stem cells right where they need to go. Using two methods of targeting the magnet and the antibodies improves the chances of being able to bring a large number of stem cells at the site of injury.

In addition to providing a way to physically move the stem cells to the heart, the iron nanoparticles are visible on MRI machines, which allows MagBICE to be visualized after its infused into the bloodstream.

Cheng doesnt foresee much toxicity from the nanomedicine unless someone is allergic or particularly sensitive to iron. In fact, the iron-based nanoparticle that forms the platform for the antibodies is an FDA-approved IV treatment for anemia.

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Can a bodys own stem cells help heal a heart?

Nanomedicine Market – Global Industry Analysis, Size, Share,Growth, Trends and Forecast, 2013 20 – Video


Nanomedicine Market - Global Industry Analysis, Size, Share,Growth, Trends and Forecast, 2013 20
http://my.brainshark.com/Nanomedicine-Market-Global-Industry-Analysis-Size-Share-Growth-Trends-and-Forecast-2013-2019-32554938 - Transparency Market Research...

By: Alina Martin

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Nanomedicine Market - Global Industry Analysis, Size, Share,Growth, Trends and Forecast, 2013 20 - Video

The Cutting Edge of Science, Homeopathy and Nanomedicine w/ Dana Ullman, MPH, CCH — Part I (of V) – Video


The Cutting Edge of Science, Homeopathy and Nanomedicine w/ Dana Ullman, MPH, CCH -- Part I (of V)
A presentation at San Francisco #39;s prestigious Commonwealth Club (September 17, 2014). The body of evidence for homeopathy and nanopharmacology is so much larger than most people realize, ...

By: Dana Ullman

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The Cutting Edge of Science, Homeopathy and Nanomedicine w/ Dana Ullman, MPH, CCH -- Part I (of V) - Video

Nanoparticle Synthesis Benefits From Award-winning Syrris Batch and Flow Reactors

Innovative batch and flow reactors from leading manufacturer Syrris are proving advantageous for a variety of nanoparticle applications, offering scientists working in the field numerous benefits. Simple to assemble with no tools required, the easy-to-use reactors enable conditions such as temperature, time, mixing, reagent ratios and concentrations to be quickly varied for rapid process optimization. Excellent mixing and temperature control ensure a narrow particle size distribution and, to further enhance reproducibility, the systems can be fully automated.

Batch reactors such as the modular Atlas system offer multiple sensors including temperature, pH and turbidity, and have no particle size restrictions. With a large choice of reactor sizes, process scale-up is straightforward. One company successfully performing batch synthesis of nanoparticles is Spanish nanomedicine company Midatech Biogune. "Our Atlas Potassium reactors have allowed us to scale-up production, enabling variables such as pH and temperature to be tightly controlled," said CEO Justin Barry. Flow chemists have enjoyed similar success, with Paulina Lloret, a researcher at the Argentinian National Institute of Industrial Technologies, saying, "We trialed our nanoparticle experiments on the Asia flow chemistry system, and immediately placed an order for our own system to optimize the speed and results of our synthesis workflow". The flexible Asia system's fast and reproducible mixing, excellent heat transfer and accurate temperature control, plus a wide range of flow rates, allow process optimization and production on the same reactor. This high level of control has enabled synthesis of nanoparticles not previously seen using batch techniques.

Syrris Limited Syrris is world renowned for excellence in chemical reactor systems and is a world leader in flow chemistry systems. Established in 2001, Syrris employs over 30 scientists and engineers at its facility in Royston (near Cambridge, UK) and has offices in the US, Japan, India and Brazil plus over 30 distributors worldwide.

Syrris develops laboratory automation products for research and development chemists in industries such as pharma, petrochem, agrochem, fine chemical synthesis etc. as well as academia. Syrris products are used in a wide variety of applications and laboratories including process, discovery, crystallization, process safety, scale-up and many more.

Syrris products include the innovative range of fully automated batch reactor products (Atlas), a manually operated jacketed reactor platform (Globe) and flow chemistry systems (Asia and Africa). In recognition of its technological achievements, Syrris has been awarded the "Eastern Region's UKTI Best Established Exporter" and the "Most Outstanding Export Achievement" at the Global Opportunity Conference on International Trade. Syrris' Asia Flow Chemistry system was the recipient of a prestigious 2012 RD award.

2014 kdm communications limited

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Nanoparticle Synthesis Benefits From Award-winning Syrris Batch and Flow Reactors

Combining antibodies, iron nanoparticles and magnets steers stem cells to injured organs

Study published in Nature Communications details targeted nanomedicine therapy to regenerate heart muscle injured by heart attack

LOS ANGELES Researchers at the Cedars-Sinai Heart Institute infused antibody-studded iron nanoparticles into the bloodstream to treat heart attack damage. The combined nanoparticle enabled precise localization of the body's own stem cells to the injured heart muscle.

The study, which focused on laboratory rats, was published today in the online peer reviewed journal Nature Communications. The study addresses a central challenge in stem cell therapeutics: how to achieve targeted interactions between stem cells and injured cells.

Although stem cells can be a potent weapon in the fight against certain diseases, simply infusing a patient with stem cells is no guarantee the stem cells will be able to travel to the injured area and work collaboratively with the cells already there.

"Infusing stem cells into arteries in order to regenerate injured heart muscle can be inefficient," said Eduardo Marbn, MD, PhD, director of the Cedars-Sinai Heart Institute, who led the research team. "Because the heart is continuously pumping, the stem cells can be pushed out of the heart chamber before they even get a chance to begin to heal the injury."

In an attempt to target healing stem cells to the site of the injury, researchers coated iron nanoparticles with two kinds of antibodies, proteins that recognize and bind specifically to stem cells and to injured cells in the body. After the nanoparticles were infused into the bloodstream, they successfully tracked to the injured area and initiated healing.

"The result is a kind of molecular matchmaking," Marbn said. "Through magnetic resonance imaging, we were able to see the iron-tagged cells traveling to the site of injury where the healing could begin. Furthermore, targeting was enhanced even further by placing a magnet above the injured heart."

The Cedars-Sinai Heart Institute has been at the forefront of developing investigational stem cell treatments for heart attack patients. In 2009, Marbn and his team completed the world's first procedure in which a patient's own heart tissue was used to grow specialized heart stem cells. The specialized cells were then injected back into the patient's heart in an effort to repair and regrow healthy muscle in a heart that had been injured by a heart attack. Results, published in The Lancet in 2012, showed that one year after receiving the stem cell treatment, heart attack patients demonstrated a significant reduction in the size of the scar left on the heart muscle.

Earlier this year, Heart Institute researchers began a new study, called ALLSTAR, in which heart attack patients are being infused with allogeneic stem cells, which are derived from donor-quality hearts.

The process to grow cardiac-derived stem cells was developed by Dr. Marbn when he was on the faculty of Johns Hopkins University. Johns Hopkins has filed for a patent on that intellectual property and has licensed it to Capricor, a company in which Cedars-Sinai and Dr. Marbn have a financial interest. Capricor is providing funds for the ALLSTAR clinical trial at Cedars-Sinai. Recently, the Heart Institute opened the nation's first Regenerative Medicine Clinic, designed to match heart and vascular disease patients with appropriate stem cell clinical trials being conducted at Cedars-Sinai and other institutions.

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Combining antibodies, iron nanoparticles and magnets steers stem cells to injured organs

IBM’s ‘Ninja Particles’ could stop the rise of superbugs

IBM Research's Jim Hedrick has a great job. His work on polymers -- those repeating chains of macromolecules that make up most things in our world, like the computer or phone you're reading this on -- has led to the creation of substances with Marvel Comics-worthy descriptors. There's the self-healing, Wolverine-like substance that arose from a recycled water bottle and something called "ninja particles" that'll advance the reality of nanomedicine. Both discoveries will inevitably make their way into consumer products in the near future, but it's his team's progress on nanomedicine that Hedrick discussed during my visit to IBM Research's sprawling Almaden lab in San Jose, California.

The inspiration for IBM's foray into nanomedicine is twofold: our growing resistance to antibiotics and the incidence of medical-implant rejection by the human body. With this in mind, Hedrick and his team, leveraging IBM's background in semiconductor research, developed synthetic polymers that mimic the immune system. Using a simple charge, these resultant polymers are capable of hunting down and clinging to specific microbes throughout the body. And, once attached, cause those microbes to rupture as if they'd been hit by an explosive shuriken (or ninja star) -- hence, the name.

Of course, anyone who's seen Innerspace knows there's a certain danger to injecting foreign objects into your body. But Hedrick says we have nothing to worry about. The ninja particles won't pass into other parts of the body. They're also proven to have a low toxicity and, best of all, won't engender a new wave of resistant pathogens (read: superbugs). So when will see the practical fruits of IBM's research? Well, Hedrick tells us the company's already in talks with various partners to apply this nanotech to our modern world in anything from medicine to the deodorant we use daily to the detergents we use to wash our clothes and kitchenware. And that future's not too far off, either -- Hedrick believes we could begin to see these ninja particle-infused products hit retail within a decade's time.

Watch Hedrick explain how IBM's research into ninja particles can help revolutionize the health care industry.

Stay tuned for part three of our inside look at IBM's Almaden research facility.

[Image credit: Laguna Design/Getty]

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IBM's 'Ninja Particles' could stop the rise of superbugs

Fantastic voyage in nanomedicine takes us into realm of science fiction

In 1966, scientists made a huge breakthrough in nanomedicine. They found they could miniaturise a submarine and its crew and inject it into a patients bloodstream. The sub then wound its way through the patients body till it reached the brain, where the crew could then destroy a blood clot using laser guns.

Of course, this was pure science fiction. It was the plot of the movie Fantastic Voyage, a phantasmagorical thriller in which the intrepid crew of the Proteus had just one hour to save the life of a top scientist, while avoiding such dangers as voracious white blood cells, lymph nodes and enemy spies. As a kid, I was enthralled by the film: secret agents, giant man-eating antibodies, and Raquel Welch as a sexy scientist it was a boys own fantasy.

In real life, were a long way from shrinking people and sending them inside someones body to carry out surgical procedures. But we are able to use nanoparticles as intravenous couriers to deliver drugs to specific parts of the body, or to sneak tiny Trojan horses into cancerous cells to destroy them from the inside.

In Ireland, pioneering research into nanomed is being done at Crann, the Centre for Research on Adaptive Nanostructures and Nanodevices, Trinitys largest research institute.

Two leaders in the field of nanomedicine, Prof Yuri Volkov, chair of molecular and translational medicine and director of research at the TCD School of Medicine, and Prof Adriele Prina-Mello, are working together to develop ways to accurately attack illness using nanomaterials. Prof Volkov, whose team was working with cells and molecules and signalling processes, joined up with Prof Prina-Mello, whose team were perfecting nanomaterials.

It was the result of an opening up of a large-scale interdisciplinary collaboration within the college. And it merged into something where you can apply those nanoparticles for treatment and benefit in the biomedical setting. Thats how its developed, says Prof Volkov.

Prof Volkov also co-ordinates a Europe-wide consortium called Namdiatream, which co-ordinates expertise from around the EU to create nanotech toolkits for early diagnosis and treatment of cancer.

Nanomedicine is a relatively young science, but already it is making great strides, and, says Prof Volkov, nanoparticles are already being used to target disease at the cellular and even molecular level.

We are dealing with very small structures which are positioned in between the individual atoms, and small biological molecules such as proteins, says Prof Volkov.

Were talking about yokes a mere handful of atoms thick you wouldnt be using a tweezers. So how do you manipulate nanomaterials, and how can you even see whats going on at that level?

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Fantastic voyage in nanomedicine takes us into realm of science fiction

New knowledge of cannabis paves way for drug development

About 40% of all medicines used today work through the so-called "G protein-coupled receptors." These receptors react to changes in the cell environment, for example, to increased amounts of chemicals like cannabis, adrenaline or the medications we take and are therefore of paramount importance to the pharmaceutical industry.

"There is a lot of attention on research into "G protein-coupled receptors," because they have a key roll in recognizing and binding different substances. Our new method is of interest to the industry because it can contribute to faster and cheaper drug development," explains Professor Dimitrios Stamou, who heads the Nanomedicine research group at the Nano-Science Center, where the method has been developed. The new method is described in a publication at the esteemed scientific journal Nature Methods.

Cheaper to test and develop medicine

The new method will reduce dramatically the use of precious membrane protein samples. Traditionally, you test a medicinal substance by using small drops of a sample containing the protein that the medicine binds to. If you look closely enough however, each drop is composed of thousands of billions of small nano-containers containing the isolated proteins. Until now, it has been assumed that all of these nano-containers are identical. But it turns out this is not the case and that is why researchers can use a billion times smaller samples for testing drug candidates than hitherto.

"We have discovered that each one of the countless nano-containers is unique. Our method allows us to collect information about each individual nano-container. We can use this information to construct high-throughput screens, where you can, for example, test how medicinal drugs bind G protein-coupled receptors," explains Signe Mathiasen, who is first author of the paper describing the screening method in Nature Methods. Signe Mathiasen has worked on developing a screening method over the last four years at the University of Copenhagen, where she wrote her PhD thesis research project under the supervision of Professor Stamou.

Story Source:

The above story is based on materials provided by Faculty of Science - University of Copenhagen. Note: Materials may be edited for content and length.

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New knowledge of cannabis paves way for drug development