Targeted Multidrug Delivery Systems To Kill Antibiotic-Resistant Staphylococcus Aureus

Abstract

Different ordered mesoporous silica (OMS) nanoparticles, ranging from regular COK-12 to COK-12 modified in terms of pore shape and size, have been employed as standard drug carriers for the controlled adsorption and release of drug molecules in comparison to well-known OMS SBA-15 and MCM-41. The cytotoxicity analysis demonstrated that regular COK-12 particles were less harmful to mammalian cultured cells, causing lower apoptosis induction than modified COK-12, MCM-41, and SBA-15 particles. Thus, regular COK-12 was further used to prepare a dual antibiotic-loaded drug delivery material, followed by surface functionalization with Staphylococcus aureus-specific aptamers for targeting. The results demonstrated that the joint loading of lysozyme and vancomycin in regular COK-12 improved the ability of the antibiotic treatments to kill methicillin-resistant Staphylococcus strains via aptamer targeting. The minimum inhibitory concentration (MIC) values decreased 4.1-fold and 12-fold compared to the non-targeted use of the antimicrobial agents in homogeneous solutions for vancomycin and lysozyme, respectively, clearly demonstrating the high potential of COK-12 to be used as a carrier in multidrug therapy. © 2023 Elsevier B.V.