Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200125, China.
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200125, China.
Acta Biomater. 2022 Sep 15;150:380-390. doi: 10.1016/j.actbio.2022.07.046. Epub 2022 Jul 30.
Infections caused by drug-resistant bacteria pose a great threat to human health. Non-antibiotic-dependent antibacterial strategies have become the focus of research. Among them, chemical dynamic treatment-based (CDT) therapeutic systems, which catalyze the production of hydroxyl radicals by enzymes, have achieved tremendous success for antibacterial purposes. However, limited kinetics of the Fenton reaction, poor permeability, and short half-life of hydroxyl radicals compromise the antibacterial effects of CDT. In addition, difficulties in the early diagnosis of infection lead to drug abuse and delayed treatment. Herein, a polydopamine coated ferrous sulfide theranostic platform adsorbing a hypochlorite responsive probe with photothermal treatment (PTT) enhanced CDT was synthesized. The probe component was used for the early diagnosis of infection. PTT not only inactivated bacteria by hyperthermia but also accelerated the Fenton reaction to produce more ·OH. In vitro antibacterial experiments demonstrated that the multifunctional theranostic platform has a broad antibacterial spectrum, including methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Escherichia coli (DR E. coli), and Pseudomonas aeruginosa (P. aeruginosa). In addition, in vivo antibacterial experiments demonstrated that nanoparticles could effectively rescue S. aureus-infected full-thickness skin defects with negligible cytotoxicity. This study proposes an efficient and multifunctional theranostic platform for bacterial infection, providing an effective synergistic antibacterial strategy for the treatment of antibiotic resistance. STATEMENT OF SIGNIFICANCE: An infection responsive theranostic platform (ClO probe@FeS@PDA) is prepared. ·CDT is enhanced prominently by PTT at a relative low temperature. · FeS@PDA exhibits good antibacterial performance against drug resistant bacteria in vitro and in vivo.
耐药菌引起的感染对人类健康构成了巨大威胁。非抗生素依赖的抗菌策略已成为研究的焦点。其中,基于化学动力学治疗(CDT)的治疗系统通过酶催化产生羟基自由基,在抗菌方面取得了巨大成功。然而,Fenton 反应的动力学有限、羟基自由基的通透性差和半衰期短,限制了 CDT 的抗菌效果。此外,感染的早期诊断困难导致了药物滥用和治疗延误。在此,合成了一种聚多巴胺包覆的硫化亚铁治疗诊断一体化平台,该平台吸附了一种对次氯酸盐有响应的探针,并具有光热治疗(PTT)增强的 CDT。探针组件用于感染的早期诊断。PTT 不仅通过高热使细菌失活,还加速了 Fenton 反应以产生更多的·OH。体外抗菌实验表明,多功能治疗诊断一体化平台具有广谱抗菌活性,包括耐甲氧西林金黄色葡萄球菌(MRSA)、耐药大肠杆菌(DR E. coli)和铜绿假单胞菌(P. aeruginosa)。此外,体内抗菌实验表明,纳米颗粒可以有效地挽救金黄色葡萄球菌感染的全厚皮肤缺陷,且细胞毒性可忽略不计。本研究提出了一种高效多功能的治疗诊断一体化平台,为治疗抗生素耐药菌感染提供了一种有效的协同抗菌策略。