Enzyme-Responsive Polymeric Vesicles for Bacterial-Strain-Selective Delivery of Antimicrobial Agents.
Antimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain-selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase (PGA) and β-lactamase (Bla), which are closely associated with drug-resistant bacterial strains, antibiotic-loaded polymeric vesicles undergo self-immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain-selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β-lactam antibiotic drugs, as a further validation, we demonstrate methicillin-resistant S. aureus (MRSA)-triggered release of antibiotics from Bla-degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.
['Li|Yamin|Y|', 'Liu|Guhuan|G|', 'Wang|Xiaorui|X|', 'Hu|Jinming|J|', 'Liu|Shiyong|S|http://orcid.org/0000-0002-9789-6282']
D000890:Anti-Infective Agents D055624:Methicillin-Resistant Staphylococcus aureus D008826:Microbial Sensitivity Tests D008854:Microscopy, Electron D011108:Polymers D013050:Spectrometry, Fluorescence
enzyme-responsive polymeric vesicles β-lactamase antibiotic resistance block copolymers