Biodegradable nanostructures with selective lysis of microbial membranes
Author: ["Fredrik Nederberg","Ying Zhang","Jeremy P. K. Tan","Kaijin Xu","Huaying Wang","Chuan Yang","Shujun Gao","Xin Dong Guo","Kazuki Fukushima","Lanjuan Li","James L. Hedrick","Yi-Yan Yang"]
Publication: Nature Chemistry
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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. Macromolecules with antimicrobial properties are promising materials for combating multi-drug-resistant microbes. Now, it has been shown that amphiphilic cationic polycarbonates that are biodegradable can self-assemble into micellar nanoparticles that can kill gram-positive bacteria, MRSA and fungi efficiently, even at low concentrations. Moreover, no significant toxicity is observed during in vivo studies in mice.
Cite this article
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
