Biodegradable polycaprolactone metallopolymer-antibiotic bioconjugates containing phenylboronic acid and cobaltocenium for antimicrobial application

用于抗菌应用的含苯硼酸和钴茂的可生物降解聚己内酯金属聚合物-抗生素生物缀合物

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Abstract

This paper reports antimicrobial metallopolymers containing biodegradable polycaprolactone as the backbone with boronic acid and cobaltocenium as the side chain. While boronic acid promotes interactions with bacterial cells via boronolectin with lipopolysaccharides, cationic cobaltocenium facilitates the unique complexation with anionic β-lactam antibiotics. The synergistic interactions in these metallopolymer-antibiotic bioconjugates were evidenced by re-sensitized efficacy of penicillin-G against four different Gram-negative bacteria (E. coli, P. vulgaris, P. aeruginosa and K. pneumoniae). The degradability of the polyester backbone was validated through tests under physiological pH (7.4) and acidic pH (5.5) or under enzymatic conditions. These metallopolymers exhibited time-dependent uptake and reduction of cobalt metals in different organs of mice via in vivo absorption, distribution, metabolism, and excretion (ADME) tests.

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