Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu, 215123, China.
Children's Hospital of Soochow University, Pediatric Research Institute of Soochow University, Suzhou, Jiangsu, 215123, China.
Small. 2020 Jul;16(28):e2000589. doi: 10.1002/smll.202000589. Epub 2020 Jun 10.
The emergence of drug-resistant bacteria and easy recurrence has been challenging in the clinical treatment of skin abscesses resulting from bacterial infections (e.g., by Staphylococcus aureus (S. aureus)). Herein, an antibacterial nanoagent capable of modulating the abscess microenvironment is designed to enhance photodynamic treatment of skin abscesses, and subsequently activate the immune system to effectively prevent abscess recurrence. In the system, manganese dioxide nanoparticles (MnO NPs) with high catalytic reactivity toward H O are modified with photosensitizer chlorine e6 (Ce6) and coated with polyethylene glycol (PEG). The obtained Ce6@MnO -PEG NPs, by triggering the decomposition of lesion endogenous H O , are able to effectively relieve the hypoxic abscess microenvironment during S. aureus infection. The light-triggered photodynamic bacterial killing effect could thus be remarkably enhanced, resulting in effective in vivo therapy of S. aureus-induced skin abscesses. Interestingly, a notable pathogen-specific immunological memory effect against future infection by the same species of bacteria is elicited after such treatment, owing to the release of bacterial antigens post photodynamic therapy (PDT) together with the adjuvant-like function of manganese ions to activate the host immune system. This work thus presents a new type of photodynamic nanoagent particularly promising for highly effective light-triggered abscess treatment and prevention of abscess recurrence.
耐药菌的出现和易复发一直是细菌感染(例如金黄色葡萄球菌(S. aureus))导致皮肤脓肿临床治疗的挑战。在此,设计了一种能够调节脓肿微环境的抗菌纳米制剂,以增强光动力治疗皮肤脓肿,并随后激活免疫系统,有效预防脓肿复发。在该系统中,对 H O 具有高催化活性的二氧化锰纳米颗粒(MnO NPs)用光敏剂氯 e6(Ce6)进行修饰,并涂覆有聚乙二醇(PEG)。所获得的 Ce6@MnO-PEG NPs 通过触发病变内源性 H O 的分解,能够有效缓解金黄色葡萄球菌感染期间的缺氧脓肿微环境。因此,光触发的光动力杀菌效果可以显著增强,从而有效治疗金黄色葡萄球菌诱导的皮肤脓肿。有趣的是,在进行这种治疗后,会引发针对同种细菌未来感染的明显的病原体特异性免疫记忆效应,这是由于光动力疗法(PDT)后释放细菌抗原以及锰离子的佐剂样功能激活了宿主免疫系统。因此,这项工作提出了一种新型的光动力纳米制剂,特别有希望用于高效的光触发脓肿治疗和预防脓肿复发。