Making vancomycin a potent broad-spectrum antimicrobial agent using polyaziridine-stabilized gold nanoparticles as a delivery vehicle.

The rise of antimicrobial drug resistance among microorganisms presents a global challenge to clinicians. Therefore, it is essential to investigate drug delivery systems to combat resistant bacteria and fungi. This study examined the potential and mode of action of vancomycin-conjugated gold nanoparticles (PEI-AuNP@Van) to enhance vancomycin's biocidal activity against <em>C. tropicalis, C. albicans, E. coli</em>, and <em>P. aeruginosa</em>. Drug conjugation and nanoparticle characterization were assessed using UV-Vis spectroscopy, X-ray diffraction, TEM, ATR-FTIR, and fluorescence spectroscopy. Effective vancomycin conjugation on polyethyleneimine-stabilized gold nanoparticles was achieved via electrostatic interactions or hydrogen bonding between the COO-/OH groups of vancomycin and the NH- groups of polyethyleneimine, yielding nanoparticles with a narrow size distribution and high zeta potential. The high luminescence of the nanoparticles facilitated their detection in microbial cells. PEI-AuNP@Van was internalized in <em>C. albicans</em> and <em>C. tropicalis</em> but showed surface adsorption in <em>E. coli</em> and <em>P. aeruginosa</em>. The in vitro results indicated that the nanodelivery system exhibited superior biocidal activity against the tested strains compared to free vancomycin and unconjugated AuNPs. The mode of action of PEI-AuNP@Van was cell-type-dependent, involving intracellular reactive oxygen species accumulation, cell membrane integrity loss, and apoptosis. The development of antimicrobial nanoformulations using AuNPs and efficient conjugation systems offers a promising approach to address antimicrobial drug resistance.