A magnetic-guided nano-antibacterial platform for alternating magnetic field controlled vancomycin release in staphylococcus aureus biofilm eradication.

Abstract

Bacterial resilience within biofilms, rendering them up to 1000 times more resistant to antibiotic drugs, poses a formidable challenge. This study introduces a targeted biofilm eradication strategy, termed "target-penetration-killing-eradication", implemented through magnetic micro-robotic technology. Specifically, we present the development of a magnetic-guided nano-antibacterial platform designed for alternating magnetic field (AMF) controlled vancomycin release in the eradication of Staphylococcus aureus biofilms. To address the issue of premature vancomycin release in physiological conditions, we employed a temperature-sensitive linking agent, 4,4'-azobis(4-cyano valeric acid), facilitating the conjugation of vancomycin onto Fe₃O₄/CS nanocomposites, resulting in the novel construct Fe₃O₄@CS-ACVA-VH. The release mechanism adheres to first-order kinetics and Fickian diffusion, with each 10-min AMF treatment releasing approximately 8.4 ± 1.1% of vancomycin. The potency of vancomycin in the release solution was similar to that of the original drug (MIC: 7.4 ± 3.5 vs. 5.6 μg/mL). Fe₃O₄@CS-ACVA-VH exhibited sustained antibacterial efficacy, inhibiting bacterial growth for four consecutive days and preventing the formation of bacterial biofilms on its surface. Contact-inhibition bacterial activity of Fe₃O₄@CS-ACVA-VH against S. aureus was 0.046875 mg/mL. Conceptually validating our approach, we emphasize Fe₃O₄@CS-ACVA-VH's exceptional ability to penetrate S. aureus biofilms under static magnetic field attraction. Furthermore, the nano-platform offers the unique advantage of on-demand vancomycin release through alternating magnetic field stimulation, effectively clearing a larger biofilm area. This multifunctional nano-platform demonstrates magnetic-guided biofilm penetration followed by controlled vancomycin release, presenting a promising strategy for enhanced biofilm eradication.