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Biodegradable nanostructures with selective lysis of microbial membranes

Nature Chemistry volume 3, pages 409–414 (2011)Cite this article

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Abstract

Macromolecular antimicrobial agents such as cationic polymers and peptides have recently been under an increased level of scrutiny because they can combat multi-drug-resistant microbes. Most of these polymers are non-biodegradable and are designed to mimic the facially amphiphilic structure of peptides so that they may form a secondary structure on interaction with negatively charged microbial membranes. The resulting secondary structure can insert into and disintegrate the cell membrane after recruiting additional polymer molecules. Here, we report the first biodegradable and in vivo applicable antimicrobial polymer nanoparticles synthesized by metal-free organocatalytic ring-opening polymerization of functional cyclic carbonate. We demonstrate that the nanoparticles disrupt microbial walls/membranes selectively and efficiently, thus inhibiting the growth of Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and fungi, without inducing significant haemolysis over a wide range of concentrations. These biodegradable nanoparticles, which can be synthesized in large quantities and at low cost, are promising as antimicrobial drugs, and can be used to treat various infectious diseases such as MRSA-associated infections, which are often linked with high mortality.

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Figure 1: Synthesis and micelle formation of cationic amphiphilic polycarbonates.
Figure 2: Dose-dependent growth inhibition of a range of bacteria and a fungus in the presence of polymer 3.
Figure 3: Comparative TEM images of microbes in the absence and presence of polymer 3.

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Acknowledgements

This research was supported by the National Science Foundation (NSF) Center for Polymer Interface and Macromolecular Assemblies (CPIMA; NSF-DMR-0213618) and the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore). F.N. thanks the Swedish research council (VR) for financial support.

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Author notes

  1. Fredrik Nederberg

    Present address: Present address: DuPont Central Research and Development, Experimental Station, Wilmington, Delaware 19880, USA,

  2. Fredrik Nederberg, Ying Zhang, Jeremy P. K. Tan and Kaijin Xu: These authors contributed equally to this work

Authors and Affiliations

  1. IBM Almaden Research Center, 650 Harry Road, San Jose, 95120, California, USA

    Fredrik Nederberg, Kazuki Fukushima & James L. Hedrick

  2. Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore

    Ying Zhang, Jeremy P. K. Tan, Chuan Yang, Shujun Gao & Yi-Yan Yang

  3. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China

    Kaijin Xu, Huaying Wang & Lanjuan Li

  4. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P. R. China

    Xin Dong Guo

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Contributions

J.L.H. and Y.Y.Y. conceived and designed the study. F.N., K.F. and C.Y. synthesized and characterized the polymers. Y.Z., J.P.K.T., K.X. and H.W. performed in vitro experiments, and S.G. carried out in vivo experiments. S.G., K.X., H.W. and L.L. contributed to in vivo data analysis. X.D.G. performed the simulation. J.L.H. and Y.Y.Y. wrote the paper, with contributions from the other authors for the Methods.

Corresponding authors

Correspondence to James L. Hedrick or Yi-Yan Yang.

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The authors declare no competing financial interests.

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Nederberg, F., Zhang, Y., Tan, J. et al. Biodegradable nanostructures with selective lysis of microbial membranes. Nature Chem 3, 409–414 (2011). https://doi.org/10.1038/nchem.1012

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