Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity

Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly­(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG)...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2015-12, Vol.7 (50), p.27602-27607
Main Authors: Xu, Lulu, He, Chen, Hui, Liwei, Xie, Yuntao, Li, Jia-Min, He, Wei-Dong, Yang, Lihua
Format: Article
Language:English
Subjects:
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - pharmacology
Bacteria - drug effects
Bacteria - pathogenicity
Dendrimers - chemistry
Dendrimers - pharmacology
Drug Carriers - chemistry
Drug Carriers - pharmacology
Ethylene Glycols - chemistry
Ethylene Glycols - pharmacokinetics
Humans
Lipase - antagonists & inhibitors
Lipase - chemistry
Nanoparticles - chemistry
Polyesters - chemistry
Polyesters - pharmacokinetics
Proteolysis - drug effects
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Summary:Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly­(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at ≤8 μg/mL. The observed activity may be attributed PCL’s responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at ≥2048 μg/mL. suggesting good blood compatibility required for intravenous administration.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.5b09581