Environmentally Benign Nanoantibiotics with a Built-In Deactivation Switch Responsive to Natural Habitats.

Abstract

The massive use of antibiotics in healthcare and agriculture has led to their artificial accumulation in natural habitats, which risks the structure and function of microbial community in ecosystems, threatens food and water security, and accelerates the development of resistome. Ideally, antibiotics should remain fully active in clinical services while become deactivated rapidly once released into environment, but none of the current antibiotics meet this criterion. Here we show a nanoantibiotic design that epitomizes the concept of carrying a built-in "OFF" switch responsive to natural stimuli. The environmentally benign nanoantibiotics consist of cellulose backbones covalently grafted with hydrophilic polymer brushes that by themselves are antimicrobial inactive. In their nanostructured forms in services, these cellulose-based polymer molecular brushes are potent killers for both Gram-positive and Gram-negative bacteria, including clinical multidrug resistant strains; after services and being discharged into environment, they are shredded into antimicrobial-inactive pieces by cellulases that do not exist in human body but are abundant in natural habitats. This study illuminates a new concept of mitigating the environmental footprints of antibiotics with rationally designed nanoantibiotics that can be dismantled and disabled by bioorthogonal chemistry occurring exclusively in natural habitats.

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Identifiers

DOI

10.1021/acs.biomac.0c00163

Journal

Biomacromolecules

Year

2020