<br>超声响应镓原卟啉和载氧全氟戊烷纳米液滴可有效声动力治疗植入物感染,Nanoscale

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超声响应镓原卟啉和载氧全氟戊烷纳米液滴可有效声动力治疗植入物感染
Nanoscale ( IF 5.8 ) Pub Date : 2024-05-24 , DOI: 10.1039/d4nr01244e
Kaili Yang _{1,

2} , Xiaolong Chen ₁ , Jianguang Li ₁ , Weijun Xiu ₁ , Lihui Yuwen ₁ , Jingyang Shan ₁ , Heng Dong ₃ , Shao Su ₁ , Lianhui Wang ₁

Affiliation

种植体感染是临床治疗中的严重并发症，通常伴随着具有高抗生素耐药性的细菌生物膜的形成。声动力疗法 (SDT) 是一种不含抗生素的方法，可在超声波 (US) 治疗下产生活性氧 (ROS) 来杀死细菌。然而，细菌生物膜的胞外聚合物（EPS）屏障和缺氧微环境显着限制了SDT的抗生物膜活性。在本研究中，开发了负载镓原卟啉 IX (GaPPIX) 和氧气 (O ₂ ) (LPGO ND) 的脂壳全氟戊烷 (PFP) 纳米滴，用于治疗植入物感染。在美国的刺激下，LPGO ND 会经历空化效应，并由于液-气相变而像炸弹一样破坏生物膜结构。同时，LPGO ND 在 US 刺激下释放 O ₂和 GaPPIX。释放的O ₂可以缓解生物膜中的缺氧微环境，并增强GaPPIX的ROS形成，从而增强细菌杀灭作用。体内实验结果表明，LPGO NDs 可以通过破坏生物膜结构、缓解缺氧和增强 SDT 的细菌杀灭作用，有效治疗小鼠模型中耐甲氧西林金黄色葡萄球菌(MRSA) 的植入感染。因此，这项工作提供了一种新型多功能声敏剂来克服SDT治疗种植体感染的局限性。

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

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 (O₂) (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 O₂ and GaPPIX upon US stimulation. The released O₂ can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (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.

更新日期：2024-05-24

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