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|Figure 1: Transmission Electron Microscope (TEM) image of the MRSA cell before treatment.
Figure 2: TEM image of the damaged cell wall and membrane of MRSA after treatment with biodegradable antimicrobial polymer nanoparticles.
Scientists at the Institute of Bioengineering and Nanotechnology (IBN) and IBM Research - Almaden have developed the first biodegradable polymer nanoparticles to combat drug-resistant superbugs, such as Methicillin-Resistant Staphylococcus aureus (MRSA). These nanoparticles can selectively kill the bacteria without destroying healthy red blood cells, and being biodegradable, have great potential to treat infectious diseases in the body. This was reported today in the leading scientific journal, Nature Chemistry [(2011) DOI: 10.1038/nchem.1012].
According to Dr Yiyan Yang, IBN Group Leader and one of the project's lead scientists, "Our antimicrobial polymers can successfully inhibit the growth of antibiotic-resistant bacteria without inducing hemolysis or causing significant toxicity because only a low concentration would be required. In addition, unlike existing polymers that do not form a secondary structure before interacting with the microbial membrane, our polymers can easily self-assemble into nanoparticles when dissolved in water to eradicate the bacteria completely."
The global market for infectious disease treatment was US$90.4 billion in 2009, and is projected to reach US$138 billion in 2014. The largest market share belongs to antibiotic treatments for bacterial and fungal diseases with 53% of the total infectious disease treatment market. 1 The development of stronger strains of bacteria that are resistant to conventional antibiotics, and a lack of safe and efficient products to treat multidrug-resistant bacterial infections pose major challenges for this field. In the United States alone in 2005, almost 95,000 people contracted serious MRSA infections and an estimated 19,000 were killed from this hospital stay-related infection. 2
To address this increasingly widespread healthcare problem, the global research community has been investigating the use of synthetic polymers with antimicrobial properties to overcome the drawbacks of the antibiotic delivery mechanism. Conventional antibiotics penetrate the microorganisms without damaging the bacteria structure (cell wall and membrane). Hence, the bacteria can easily develop resistance against these drugs. In comparison, antimicrobial polymers break down the bacterial cell wall and membrane based on electrostatic interaction with the bacteria to prevent drug resistance.
A major side effect caused by many existing antimicrobial polymers is hemolysis, the breakdown of red blood cells, in addition to the infected cells. Most antimicrobial polymers are also non-biodegradable, which limits their in vivo applications as they cannot be naturally eliminated from the body.
Scientists at IBN and IBM Research have now successfully developed a new biodegradable and in vivo applicable antimicrobial polymer, which can selectively eliminate the bacteria without destroying the surrounding healthy red blood cells. This research discovery was first conceived in 2007 and the antimicrobial polymers were tested against clinical microbial samples by the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University in China.
"Over the last four years, we've worked with IBN to understand and define a specific problem such as infectious disease and then collaborate on the design and characterization of a new polymer-based solution that improves upon existing treatment options," said Dr James Hedrick, Advanced Organic Materials Scientist, IBM Research - Almaden. "This breakthrough in antimicrobial research represents another example of how scientists are expanding beyond traditional boundaries by applying lessons learned from other research fields. Our combined materials development and bioengineering expertise enabled us to discover a new way to potentially treat infectious diseases."
Professor Jackie Y. Ying, IBN Executive Director, shared, "This exciting platform technology can make a significant impact on the treatment of multidrug-resistant bacteria. IBN actively pursues research collaboration to address important healthcare problems in the world as we believe that technological breakthroughs will occur when they are built upon shared expertise and strengths between research organizations, clinicians, academia and industry. Our collaboration with IBM is an excellent example of how our strategic partnership with a corporate research laboratory is able to create an innovative biomedical solution."
The starting materials of the novel polymer are inexpensive and the synthesis is simple and scalable for future clinical applications. These biodegradable nanoparticles could be topically applied to the skin or injected into the body to treat MRSA skin infections. It could also be developed into consumer products such as deodorants, table wipes and preservatives. Other potential applications include treatment for wound healing, multidrug-resistant tuberculosis and lung infections.
The research collaboration between IBN and IBM in the area of self-assembling synthetic polymers for biomedical applications has generated a number of novel platform technologies for drug/gene delivery and antimicrobial applications. To date, the team has filed 6 US patent applications on their research, and published 21 papers in high-impact scientific journals such as Nature Chemistry, Nano Today, Angewandte Chemie International Edition, Biomaterials, Small and Journal of Controlled Release.
F. Nederberg, Y. Zhang, J. P. K. Tan, K. Xu, H. Wang, C. Yang, S. Gao, X. D. Guo, K. Fukushima, L. J. Li, J. L. Hedrick and Y. Y. Yang, "Biodegradable Nanostructures with Selective Lysis of Microbial Membranes," Nature Chemistry, (2011) DOI:10.1038/nchem.1012.
C. Yang, J. P. K. Tan, W. Cheng, A. Bte Ebrahim Attia, C. Y. T. Tan, A. Nelson, J. L. Hedrick and Y. Y. Yang, "Supramolecular Nanostructures Designed for High Cargo Loading Capacity and Kinetic Stability," Nano Today, 5 (2010) 515-523.
S. H. Kim, F. Nederberg, R. Jakobs, J. P. K. Tan, K. Fukushima, A. Nelson, E. W. Meijer, Y. Y. Yang and J. L. Hedrick, "A Supramolecularly Assisted Transformation of Block Copolymer Micelles into Nanotubes," Angewandte Chemie International Edition, 48 (2009) 4508-4512.
S. H. Kim, J. P. K. Tan, F. Nederberg, K. Fukushima, J. Colson, A. Nelson, Yi Yan Yang and J. L. Hedrick, "Hydrogen Bonding-Enhanced Micelle Assemblies for Drug Delivery," Biomaterials, 31 (2010) 8063-8071.
F. Suriano, R. Pratt, J. P. K. Tan, N. Wiradharma, A. Nelson, Y. Y. Yang, P. Dubois and J. L. Hedrick, "Synthesis of A Family of Amphiphilic Glycopolymers via Controlled Ring-Opening Polymerization of Functionalized Cyclic Carbonates and Their Application in Drug Delivery," Biomaterials, 31 (2010) 2637-2645.
J. P. K. Tan, S. H. Kim, F. Nederberg, E. A. Appel, R. M. Waymouth, Y. Zhang, J. L. Hedrick and Y. Y. Yang, "Hierarchical Supermolecular Structures for Sustained Drug Release," Small, 5 (2009) 1504-1507.
Z. Y. Ong, K. Fukushima, D. J. Coady, Y. Y. Yang, P. L. R. Ee and J. L. Hedrick, "Rational Design of Biodegradable Cationic Polycarbonates for Gene Delivery," Journal of Controlled Release (2011) DOI: 10.1016/j.jconrel.2011.01.020.
About Institute of Bioengineering and Nanotechnology (IBN)
The Institute of Bioengineering and Nanotechnology (IBN) was established in 2003 and is spearheaded by its Executive Director, Professor Jackie Yi-Ru Ying, who has been on the Massachusetts Institute of Technology's Chemical Engineering faculty since 1992, and was among the youngest to be promoted to Professor in 2001.
In 2008, Professor Ying was recognized as one of "One Hundred Engineers of the Modern Era" by the American Institute of Chemical Engineers for her groundbreaking work on nanostructured systems, nanoporous materials and host matrices for quantum dots and wires.
Under her direction, IBN conducts research at the cutting-edge of bioengineering and nanotechnology. Its programs are geared towards linking multiple disciplines across all fields in engineering, science and medicine to produce research breakthroughs that will improve healthcare and our quality of life.
IBN's research activities are focused in the following areas:
Drug and Gene Delivery, where the controlled release of therapeutics involve the use of functionalized polymers, hydrogels and biologics for targeting diseased cells and organs, and for responding to specific biological stimuli.
Cell and Tissue Engineering, where biomimicking materials, stem cell technology, microfluidic systems and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs.
Biodevices and Diagnostics, which involve nanotechnology and microfabricated platforms for high-throughput biomarker and drug screening, automated biologics synthesis, and rapid disease diagnosis.
Pharmaceuticals Synthesis and Green Chemistry, which encompasses the efficient catalytic synthesis of chiral pharmaceuticals, and new nanocomposite materials for sustainable technology and alternative energy generation.
IBN's innovative research is aimed at creating new knowledge and intellectual properties in the emerging fields of bioengineering and nanotechnology to attract top-notch researchers and business partners to Singapore. Since 2003, IBN researchers have published over 660 papers in leading journals.
IBN also plays an active role in technology transfer and spinning off companies, linking the research institute and industrial partners to other global institutions. The Institute has filed over 1,100 patent applications on its inventions and is currently looking for partners for collaboration and commercialization of its portfolio of technologies.
IBN's current staff strength stands at over 170 scientists, engineers and medical doctors. With its multinational and multidisciplinary research staff, the institute is geared towards generating new biomaterials, devices, systems, equipment and processes to boost Singapore's economy in the fast-growing biomedical sector.
IBN is also committed to nurturing young minds, and the institute acts as a training ground for PhD students and undergraduates. In October 2003, IBN initiated a Youth Research Program to open its doors to university students, as well as students and teachers from various secondary schools and junior colleges. It has since reached out to more than 44,000 students and teachers from 235 local and overseas schools and institutions.
About IBM Research
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