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超声响应载镓原卟啉和氧的全氟戊烷纳米液滴用于植入物感染的有效声动力学治疗。

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

机构信息

State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China.

Department of Clinical Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008, Nanjing, China.

出版信息

Nanoscale. 2024 Jun 20;16(24):11669-11678. doi: 10.1039/d4nr01244e.


DOI:10.1039/d4nr01244e
PMID:38855849
Abstract

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O and GaPPIX upon US stimulation. The released O can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

摘要

植入物感染是临床治疗中的严重并发症,常伴有具有高抗生素耐药性的细菌生物膜形成。声动力学疗法(SDT)是一种无抗生素的方法,可在超声(US)治疗下产生活性氧(ROS)来杀死细菌。然而,细菌生物膜的细胞外聚合物(EPS)屏障和缺氧微环境显著限制了 SDT 的抗生物膜活性。在这项研究中,负载了原卟啉 IX 镓(GaPPIX)和氧(O)的脂质壳氟戊烷(PFP)纳米液滴(LPGO NDs)被开发用于治疗植入物感染。在 US 刺激下,LPGO NDs 经历空化效应,并由于液-气相转变而像炸弹一样破坏生物膜结构。同时,LPGO NDs 在 US 刺激下释放 O 和 GaPPIX。释放的 O 可以缓解生物膜中的缺氧微环境,并通过 GaPPIX 增强 ROS 形成,从而增强细菌杀伤作用。实验结果表明,LPGO NDs 通过破坏生物膜结构、缓解缺氧和增强 SDT 杀菌作用,可有效治疗小鼠耐甲氧西林金黄色葡萄球菌(MRSA)植入物感染。因此,这项工作提供了一种新的多功能声敏剂,以克服 SDT 治疗植入物感染的局限性。

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