Quaternary Ammonium-Tethered Phenylboronic Acids Appended Supramolecular Nanomicelles as a Promising Bacteria Targeting Carrier for Nitric Oxide Delivery

Abstract

The delivery of drugs to focal sites is a central goal and a key challenge in the development of nanomedicine carriers. This strategy can improve the selectivity and bioavailability of the drug while reducing its toxicity. To ensure the specific release of nitric oxide at the site of a bacterial infection without damaging the surrounding normal tissue, we designed a host-guest molecule containing a host molecule with a target moiety and a nitric oxide donor to release nitric oxide. The boronic acid group in the structure of this nanoparticle interacts strongly and specifically with the surface of E. coli. In addition, the quaternary amine salt can interact electrostatically with bacteria, indicating a large number of negatively charged cell membranes; altering the molecular structure of the cell membrane; increasing the permeability of the cell membrane; and causing cytoplasmic diffusion and cell lysis, resulting in lethal activity against most bacteria. The synthesised molecules were characterised by 1H NMR and mass spectrometry. The strong specific interaction of the boronic acid moiety with the surface of E. coli and the electrostatic interaction of the quaternary amine salt with the cell membrane were confirmed by antibacterial experiments on molecules with and without the targeting moiety. The targeting group-modified micelles enhanced the antibacterial effect of the micelles very effectively through specific interactions and electrostatic interactions. In addition, in vitro skin wound healing experiments also confirmed the targeting and antimicrobial effect of micelles. These results suggest that the specific release of nitric oxide at the site of bacterial infection is an important guide to further address the emergence of antibiotic-resistant strains of bacteria.