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. 2025 Jul 7;22(7):3836-3847.
doi: 10.1021/acs.molpharmaceut.5c00097. Epub 2025 Jun 6.

Efficacy Evaluation and Mechanism Study of Nonantibiotic Nanoplatform for Clearing MRSA

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Efficacy Evaluation and Mechanism Study of Nonantibiotic Nanoplatform for Clearing MRSA

Xiangjun Chen et al. Mol Pharm. .

Abstract

The effective treatment of infections induced by biofilms has remained a substantial challenge in clinical practice. Presently, there is an imperative demand for innovative antimicrobial strategies that can not only eliminate biofilms but also incorporate controlled delivery and intelligent release mechanisms. In this research, the charge-reversible nonantibiotic nanodelivery system (MPDA/AuNCs/ICG@Lip NPs) is synthesized. Initially, AuNCs and indocyanine green (ICG) were introduced onto MPDA NPs via adsorption and mesoporous loading, followed by the modification of the phospholipids on the exterior surface. Within the biofilm microenvironment, the surface charge was reversed, thereby improving its affinity for methicillin-resistant Staphylococcus aureus (MRSA) and facilitating enhanced biofilm permeability. Owing to the ultrasmall AuNCs, they were internalized by the bacteria and, in conjunction with ICG, contributed to the elevation of local ROS concentrations under the 808 nm laser. As anticipated, the in vitro findings confirmed that MPDA/AuNCs/ICG@Lip NPs demonstrated superior biofilm-clearing capabilities and antibacterial effect. In vivo experiments corroborated that MPDA/AuNCs/ICG@Lip NPs successfully targeted the cyst site and remained localized for an extended period, resulting in excellent therapeutic efficacy. This discovery offers a novel perspective for the development of nonantibiotic nanoplatform for clearing MRSA.

Keywords: AuNCs; Biofilm; MRSA; Mesoporous Polydopamine; Nonantibiotic Therapy.

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