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用于清除耐甲氧西林金黄色葡萄球菌的非抗生素纳米平台的疗效评估及机制研究

Efficacy Evaluation and Mechanism Study of Nonantibiotic Nanoplatform for Clearing MRSA.

作者信息

Chen Xiangjun, Zhang Xinzhong, Fan Qing, Cao Menglin, Zhang Sai, Li Wenting, Ma Rui, Zhang Xiuping, Hong Wei

机构信息

School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, P. R. China.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Jinan 250000, P. R. China.

出版信息

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

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 (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 findings confirmed that MPDA/AuNCs/ICG@Lip NPs demonstrated superior biofilm-clearing capabilities and antibacterial effect. 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.

摘要

生物膜引起的感染的有效治疗在临床实践中仍然是一项重大挑战。目前,迫切需要创新的抗菌策略,不仅能够消除生物膜,还能纳入可控释放和智能释放机制。在本研究中,合成了电荷可逆的非抗生素纳米递送系统(MPDA/AuNCs/ICG@Lip NPs)。首先,通过吸附和介孔负载将AuNCs和吲哚菁绿(ICG)引入MPDA NPs,随后对外表面的磷脂进行修饰。在生物膜微环境中,表面电荷发生逆转,从而提高其对耐甲氧西林金黄色葡萄球菌(MRSA)的亲和力,并促进生物膜通透性增强。由于AuNCs超小,它们被细菌内化,并与ICG一起,在808 nm激光照射下导致局部ROS浓度升高。正如预期的那样,研究结果证实MPDA/AuNCs/ICG@Lip NPs表现出卓越的生物膜清除能力和抗菌效果。实验证实MPDA/AuNCs/ICG@Lip NPs成功靶向囊肿部位并长时间保持定位,从而产生优异的治疗效果。这一发现为开发用于清除MRSA的非抗生素纳米平台提供了新视角。

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