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Abstract
Tuning the composition of antimicrobial nanogels can significantly alter both nanogel cytotoxicity and antibacterial activity. This project investigated the extent to which PEGylation of cationic, hydrophobic nanogels altered their cytotoxicity and bactericidal activity. These biodegradable, cationic nanogels were synthesized by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) emulsion polymerization with up to 13.9 wt% PEG(MW = 2,000)MA as verified by 1H NMR. Nanogel bactericidal activity was assessed against Gram-negative E. coli and P. aeruginosa and Gram-positive S. mutans and S. aureus by measuring membrane lysis with a LIVE/DEAD assay. E. coli and S. mutans viability was further validated by measuring metabolic activity with a PrestoBlue assay and imaging bacteria stained with a LIVE/DEAD probe. All tested nanogels decreased the membrane integrity (0.5 mg/mL dose) for Gram-negative E. coli and P. aeruginosa, irrespective of the extent of PEGylation. PEGylation (13.9 wt%) increased the cytocompatibility of cationic nanogels toward RAW 264.7 murine macrophages and L929 murine fibroblasts by over 100-fold, relative to control nanogels. PEGylation (42.8 wt%) reduced nanogel uptake by 43% for macrophages and 63% for fibroblasts. Therefore, PEGylation reduced nanogel toxicity to mammalian cells without significantly compromising their bactericidal activity. These results facilitate future nanogel design for perturbing the growth of Gram-negative bacteria.
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