Abstract
Antimicrobial cationic peptides are of interest because they can combat multi-drug-resistant microbes. Most peptides form α-helices or β-sheet-like structures that can insert into and subsequently disintegrate negatively charged bacterial cell surfaces. Here, we show that a novel class of core–shell nanoparticles formed by self-assembly of an amphiphilic peptide have strong antimicrobial properties against a range of bacteria, yeasts and fungi. The nanoparticles show a high therapeutic index against Staphylococcus aureus infection in mice and are more potent than their unassembled peptide counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show that the nanoparticles can cross the blood–brain barrier and suppress bacterial growth in infected brains. Taken together, these nanoparticles are promising antimicrobial agents that can be used to treat brain infections and other infectious diseases.
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Acknowledgements
The authors would like to thank J. Lu, K. Guo and S. Liu for helpful discussions. The authors are also grateful to the Clinical Testing Center, College of Medicine, Zhejiang University, P.R. China, for analysis of ALT, AST, total bilirubin, direct bilirubin, creatinine and urea nitrogen levels of the blood samples. This work was funded by the Institute of Bioengineering and Nanotechnology, Agency for Science, Technology and Research, the National Basic Research Program 973 of P.R. China (grant no. 2007cb513003) and the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, College of Medicine, Zhejiang University, P.R. China (grant no. 2008A05).
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Y.Y.Y. oversaw the project. Y.Y.Y. and L. Liu designed the peptides and peptide nanoparticles. L. Liu and J.T.P.K. synthesized and characterized the peptide nanoparticles. L. Liu, K.X. and H.W. performed the in vitro experiments. L.L., K.X., H.W. and W.F. contributed to the in vivo experiments and data analysis. Y.Y.Y. wrote the paper with contributions from L. Liu. The other authors gave suggestions to improve the presentation of the paper and prepared the Methods section.
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Liu, L., Xu, K., Wang, H. et al. Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent. Nature Nanotech 4, 457–463 (2009). https://doi.org/10.1038/nnano.2009.153
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DOI: https://doi.org/10.1038/nnano.2009.153
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