A biomimetic phage-inspired supramolecular system based on glucose-conjugated pillar[5]arene with ciprofloxacin hydrochloride

Abstract

Self-assembling phage-inspired carriers based on macrocyclic molecules have the potential to overcome antibiotic resistance and extend the antimicrobial effect of drugs. In this study, we have synthesized a new water-soluble pillar[5]arene containing thioglycoside fragments. This compound had an affinity for a model lipid membrane, underwent self-assembly, and associated with the fluoroquinolone antibiotic ciprofloxacin hydrochloride (Cipro) to form biocompatible supramolecular nanostructures. UV-vis and fluorescence spectroscopies were used to assess the ability of the pillar[5]arene/antibiotic system to form supramolecular complexes in a 1 : 2 stoichiometry (lg K_1 : 1 = 1.49 and lg K_1 : 2 = 4.22). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies confirmed the formation of stable pillararene/antibacterial complexes with particle sizes in the range of 250–300 nanometers. And the biological characteristics of the systems we obtained indicate their low toxicity to cancer (A549) and normal cells (LEK and HSF), with a twofold increase in the inhibitory effect of the combined pillar[5]arene/antibiotic system on the strain of K. pneumoniae with increased resistance to ciprofloxacin. The improved antibacterial properties of the antibiotic in combination with the pillar[5]arene may be due to the blocking of efflux pumps, which is confirmed by molecular docking.