Cucurbit[7]uril-achieved supramolecular nanoplatform capable of targeted depletion of specific pathogen for efficient bacterial keratitis therapy

Abstract

Antibacterial supramolecular nanoplatforms have attracted increasing attention in the field of biomedicine owing to their unique properties. Herein, a cucurbit[7]uril-mediated targeted supramolecular nanoparticles (MPPM⸦CB[7]) is developed to enable selective elimination of pathogenic bacteria from complex communities by using atom transfer radical polymerization (ATRP) to graft antibacterial quaternary ammonium salt monomers (1-pentyl-1-quaternary ammonium-3-vinyl-imidazole (PQVI)) and Escherichia coli (E. coli)-targeted glucosamine units (2-(methacrylamido)-glucopyranose, MAG) onto magnetic nanoparticles (MNPs), and then assembling PQVI with cucurbit[7]uril (CB[7]) via host-guest complexation. Interestingly, MPPM⸦CB[7] host–guest complex exhibits enhanced targeting toward E. coli as compared to MPPM, and the antibacterial activity is turned on through the disassembly of the MPPM⸦CB[7] host–guest complex upon the addition of competitive amantadine (AD) in situ, accompanied by efficient antibacterial performance against pathogenic bacteria Escherichia coli K12 BW25113 (10⁷ colony-forming units, 99.99 %) without harming the probiotic members Lactococcus lactis ATCC 11454 (L. lactis). Particularly, high in vivo therapeutic effectiveness is achieved in E. coli and L. lactis-induced bacterial keratitis. Besides, the magnetic recovery of MPPM reduces its residue in the body, thereby lowering the potential side effects. This CB[7]-mediated supramolecular nanoparticles may provide a new strategy for treatment of ocular disease and have the potential to replace antibiotic treatment.