UC San Diego: Targeted Drug Delivery with Nanoparticles = More Effective Medicines


Targeted Drug Delivery 150916162906_1_540x360Nanoparticles disguised as human platelets could greatly enhance the healing power of drug treatments for cardiovascular disease and systemic bacterial infections. These platelet-mimicking nanoparticles, developed by engineers at the University of California, San Diego, are capable of delivering drugs to targeted sites in the body — particularly injured blood vessels, as well as organs infected by harmful bacteria. Engineers demonstrated that by delivering the drugs just to the areas where the drugs were needed, these platelet copycats greatly increased the therapeutic effects of drugs that were administered to diseased rats and mice.

The research, led by nanoengineers at the UC San Diego Jacobs School of Engineering, was published online Sept. 16 in Nature.

“This work addresses a major challenge in the field of nanomedicine: targeted drug delivery with nanoparticles,” said Liangfang Zhang, a nanoengineering professor at UC San Diego and the senior author of the study. “Because of their targeting ability, platelet-mimicking nanoparticles can directly provide a much higher dose of medication specifically to diseased areas without saturating the entire body with drugs.”

Targeted Drug Delivery 150916162906_1_540x360

Pseudocolored scanning electron microscope images of platelet-membrane-coated nanoparticles (orange) binding to the lining of a damaged artery (left) and to MRSA bacteria (right). Each nanoparticle is approximately 100 nanometers in diameter, which is one thousand times thinner than an average sheet of paper.
Credit: Zhang Research Group, UC San Diego Jacobs School of Engineering.

The study is an excellent example of using engineering principles and technology to achieve “precision medicine,” said Shu Chien, a professor of bioengineering and medicine, director of the Institute of Engineering in Medicine at UC San Diego, and a corresponding author on the study. “While this proof of principle study demonstrates specific delivery of therapeutic agents to treat cardiovascular disease and bacterial infections, it also has broad implications for targeted therapy for other diseases such as cancer and neurological disorders,” said Chien.

The ins and outs of the platelet copycats

On the outside, platelet-mimicking nanoparticles are cloaked with human platelet membranes, which enable the nanoparticles to circulate throughout the bloodstream without being attacked by the immune system. The platelet membrane coating has another beneficial feature: it preferentially binds to damaged blood vessels and certain pathogens such as MRSA bacteria, allowing the nanoparticles to deliver and release their drug payloads specifically to these sites in the body.

Enclosed within the platelet membranes are nanoparticle cores made of a biodegradable polymer that can be safely metabolized by the body. The nanoparticles can be packed with many small drug molecules that diffuse out of the polymer core and through the platelet membrane onto their targets.

To make the platelet-membrane-coated nanoparticles, engineers first separated platelets from whole blood samples using a centrifuge. The platelets were then processed to isolate the platelet membranes from the platelet cells. Next, the platelet membranes were broken up into much smaller pieces and fused to the surface of nanoparticle cores. The resulting platelet-membrane-coated nanoparticles are approximately 100 nanometers in diameter, which is one thousand times thinner than an average sheet of paper.

This cloaking technology is based on the strategy that Zhang’s research group had developed to cloak nanoparticles in red blood cell membranes. The researchers previously demonstrated that nanoparticles disguised as red blood cells are capable of removing dangerous pore-forming toxins produced by MRSA, poisonous snake bites and bee stings from the bloodstream.

By using the body’s own platelet membranes, the researchers were able to produce platelet mimics that contain the complete set of surface receptors, antigens and proteins naturally present on platelet membranes. This is unlike other efforts, which synthesize platelet mimics that replicate one or two surface proteins of the platelet membrane.

“Our technique takes advantage of the unique natural properties of human platelet membranes, which have a natural preference to bind to certain tissues and organisms in the body,” said Zhang. This targeting ability, which red blood cell membranes do not have, makes platelet membranes extremely useful for targeted drug delivery, researchers said.

Platelet copycats at work

In one part of this study, researchers packed platelet-mimicking nanoparticles with docetaxel, a drug used to prevent scar tissue formation in the lining of damaged blood vessels, and administered them to rats afflicted with injured arteries. Researchers observed that the docetaxel-containing nanoparticles selectively collected onto the damaged sites of arteries and healed them.

When packed with a small dose of antibiotics, platelet-mimicking nanoparticles can also greatly minimize bacterial infections that have entered the bloodstream and spread to various organs in the body. Researchers injected nanoparticles containing just one-sixth the clinical dose of the antibiotic vancomycin into one of group of mice systemically infected with MRSA bacteria. The organs of these mice ended up with bacterial counts up to one thousand times lower than mice treated with the clinical dose of vancomycin alone.

“Our platelet-mimicking nanoparticles can increase the therapeutic efficacy of antibiotics because they can focus treatment on the bacteria locally without spreading drugs to healthy tissues and organs throughout the rest of the body,” said Zhang. “We hope to develop platelet-mimicking nanoparticles into new treatments for systemic bacterial infections and cardiovascular disease.”


Story Source:

The above post is reprinted from materials provided by University of California – San Diego. The original item was written by Liezel Labios. Note: Materials may be edited for content and length.


Journal Reference:

  1. Che-Ming J. Hu, Ronnie H. Fang, Kuei-Chun Wang, Brian T. Luk, Soracha Thamphiwatana, Diana Dehaini, Phu Nguyen, Pavimol Angsantikul, Cindy H. Wen, Ashley V. Kroll, Cody Carpenter, Manikantan Ramesh, Vivian Qu, Sherrina H. Patel, Jie Zhu, William Shi, Florence M. Hofman, Thomas C. Chen, Weiwei Gao, Kang Zhang, Shu Chien, Liangfang Zhang. Nanoparticle biointerfacing by platelet membrane cloaking. Nature, 2015; DOI: 10.1038/nature15373
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Research “Trio” outlines ways Nanodiamonds are being used to Treat Cancer


Nano Diamonds Cancer 090115 55dc75f7ad744A schematic of targeted drug delivery towards breast cancer is shown. Nanodiamonds are encapsulated within liposomes that are functionalized with targeting antibodies. Credit: Dr. Laura Moore (Prof. Dean Ho Group)

A trio of researchers, Dean Ho, with UCLA in the U.S., Chung-Huei Katherine Wang, with BRIM Biotechnology Inc., in Taipei and Edward Kai-Hua Chow with the National University of Singapore, has published a review in Science Advances, of the ways nanodiamonds are being used in cancer research and offer insights into the ways they may be used in the future.

As the research trio note, significant progress has been made over the past several decades in the development of nano-materials for use in treating cancer and other ailments. The central idea is to use very tiny particles to carry tumor fighting drugs to tumors (they are not as easily repelled as the larger varieties) thereby healing the patient. The list includes metallic particles, nanotubes, polymers and even lipids. More recently, scientists have been looking into using as more is learned about the electrostatic capabilities of their facet surfaces when they carry chemicals in a biological system, the ways their inert core can be useful in certain applications and as a means to capitalize on their tunable surfaces.

The authors note that nanodiamonds used in medical applications fall into two main categories, detonation nanodiamonds (DNDs) and (FNDs) as part of highlighting the major ways that nanodiamonds are currently being used:

Imaging—both DNDs and FNDs, the researchers note are increasingly being eyed as a way to improve and more recently FNDs are also being seen as a way to track stem cells to learn more about their regenerative potential.

Drug Delivery—a lot of research is currently going on to learn more about which types of drugs adhere well to nanodiamond facets, most specifically those used in chemotherapy applications.

Biodistribution and Toxicity—similarly, a lot of research is being conducted to learn more about the ways nanodiamonds can be placed into a living organism (injection, consumption, though the skin, etc.) and whether there is a danger of toxicity.

The researchers note that another area of study involves using nanodiamonds as part of drug testing—if medications can be carried to specific sites, they note, there might be less side-effects.

Another benefit of using nanodiamonds, they note, is that despite being associated with precious gems, nanodiamonds would be quite cheap to procure and use because they can be obtained from mining waste.

Explore further: Tiny diamonds to boost treatment of chemoresistant leukemia

More information: Nanodiamonds: The intersection of nanotechnology, drug development, and personalized medicine, Science Advances  21 Aug 2015: Vol. 1, no. 7, e1500439. DOI: 10.1126/sciadv.1500439

Abstract
The implementation of nanomedicine in cellular, preclinical, and clinical studies has led to exciting advances ranging from fundamental to translational, particularly in the field of cancer. Many of the current barriers in cancer treatment are being successfully addressed using nanotechnology-modified compounds. These barriers include drug resistance leading to suboptimal intratumoral retention, poor circulation times resulting in decreased efficacy, and off-target toxicity, among others.

The first clinical nanomedicine advances to overcome these issues were based on monotherapy, where small-molecule and nucleic acid delivery demonstrated substantial improvements over unmodified drug administration. Recent preclinical studies have shown that combination nanotherapies, composed of either multiple classes of nanomaterials or a single nanoplatform functionalized with several therapeutic agents, can image and treat tumors with improved efficacy over single-compound delivery. Among the many promising nanomaterials that are being developed, nanodiamonds have received increasing attention because of the unique chemical-mechanical properties on their faceted surfaces.

More recently, nanodiamond-based drug delivery has been included in the rational and systematic design of optimal therapeutic combinations using an implicitly de-risked drug development platform technology, termed Phenotypic Personalized Medicine–Drug Development (PPM-DD). The application of PPM-DD to rapidly identify globally optimized drug combinations successfully addressed a pervasive challenge confronting all aspects of drug development, both nano and non-nano. This review will examine various nanomaterials and the use of PPM-DD to optimize the efficacy and safety of current and future cancer treatment. How this platform can accelerate combinatorial nanomedicine and the broader pharmaceutical industry toward unprecedented clinical impact will also be discussed.

Lehigh University: Innovators shine at international conference


Lehigh scientists and engineers won three National Innovation Awards recently at the TechConnect 2015 World Innovation Conference and National Innovation Showcase held in Washington, D.C.

The awards were for a nanoscale device that captures tumor cells in the blood, a bioengineered enzyme that scrubs microbial biofilms, and a safe, efficient chemical reagent that is stable at room temperature.

Lehigh’s TechConnect initiative was led by the Office of Technology Transfer (OTT) which manages, protects and licenses intellectual property (IP) developed at Lehigh. Yatin Karpe, associate director of the OTT, spearheaded the Lehigh effort and is pursuing IP protection and commercialization for the innovations.

The P.C. Rossin College of Engineering and Applied Science, led by former interim Dean Daniel Lopresti, and the Office of Economic Engagement, led by assistant vice president Cameron McCoy, supported Lehigh’s third-straight appearance at the annual conference.

The three National Innovation Awards were chosen through an industry review of the top 20 percent of annually submitted technologies and based on the potential positive impact the technology would have on industry.

This is the third year in a row that Lehigh has won Innovation Awards. No institution received more than three in 2015.

Lehigh’s National Innovation Awardees were:

•    Yaling Liu, assistant professor of mechanical engineering and mechanics and a member of the bioengineering program, has developed a tiny device that can capture tumor cells circulating in the blood and can potentially indicate disease type, as well as genetic and protein markers that may provide potential treatment options.

•    Bryan Berger, assistant professor of chemical and biomolecular engineering, hopes to improve food safety and keep medical devices clean with an enzyme he’s developed that attacks biofilms.

•    David Vicic, professor and department chair of chemistry, has created a new chemical reagent that is stable at room temperature, potentially eliminating the use of traditional hazardous regents.

TechConnect is one of the largest multi-sector gatherings in the world of technology intellectual property, technology ventures, industrial partners and investors. The event brings together the world’s top technology transfer offices, companies and investment firms to identify the most promising technologies and early stage companies from across the globe.

“This event is a productive opportunity to establish new connections with industry and government partners, many within easy reach of Lehigh,” said Gene Lucadamo, the industry liaison for Lehigh’s Center for Advanced Materials and Nanotechnology and the Lehigh Nanotech Network.

“Some of these connections are with alumni in business or government, and even with nearby Pennsylvania companies that were attracted to Lehigh innovations. These interactions allow us to promote research capabilities and facilities which are available through our Industry Liaison Program, and to identify opportunities for collaborations and funding.”

In addition to the three National Innovator Awards, Lehigh researchers won seven National Innovation Showcase awards and presented five conference papers in areas as diverse as the biomanufacturing of quantum dots, a 3-D imaging technique 20 times faster than current systems, the creation of a miniature medical oxygen concentrator for patients with Chronic Obstructive Pulmonary Disease (COPD), and a biomedically superior bioactive glass that mimics bone.

Attendees include innovators, funding agencies, national and federal labs, international research organizations, universities, tech transfer offices and investment and corporate partners. The 2015 TechConnect World Innovation event encompasses the 2015 SBIR/STTR National Conference, the 2015 National Innovation Summit and Showcase, and Nanotech2015—the world’s largest nanotechnology event.

The following is a list of the Lehigh faculty members who gave presentations at TechConnect 2015:

•    A wavy micropatterned microfluidic device for capturing circulating tumor cells (Principal investigator: Liu)

•    Bioengineered enzymes that safely and cheaply fight bacterial biofilms (Principal investigator: Berger)

•    New reagents for octafluorocyclobutane transfer that eliminate the use of hazardous tetrafluoroethylene (Principal investigator: Vicic)

•    A method to cheaply manufacture quantum dots using bacteria (Principal investigator: Berger)

•    A multiplexing optical coherence tomography technology 20 times faster than current systems that preserves image resolution and allows synchronized cross-sectional and three-dimensional (3D) imaging. (Principal investigator: Chao Zhou, electrical and computer engineering)

•    A miniature medical oxygen concentrator for COPD patients (Principal investigator: Mayuresh Kothare, chemical and biomolecular engineering)

•    A biomedically superior bioactive glass that enables the production of porous bone scaffolds that can be tailored to match the tissue growth rate of a given patient type (Principal investigator: Himanshu Jain, materials science and engineering)

•    A new distributed-feedback technique that dramatically improves the laser beam patterns and increases the output power levels of semiconductor lasers (Principal investigator: Sushil Kumar, electrical and computer engineering)

•    A new pretreatment process to remove unwanted impurities in ceramic powders without any change in the physical properties, leading to better reproducibility of properties and reliability in the final products (Principal investigator: Martin Harmer, materials science and engineering)

Story by Jordan Reese