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硝态还原酶响应型纳米颗粒用于细菌性角膜炎的原位荧光成像及协同抗菌治疗。

Nitroreductase-responsive nanoparticles for in situ fluorescence imaging and synergistic antibacterial therapy of bacterial keratitis.

机构信息

Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China; Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Cixi Institute of Biomedical Engineering, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China.

Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Cixi Institute of Biomedical Engineering, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China; College of Medical Engineering & the Key Laboratory for Medical Functional Nanomaterials, Jining Medical University, Jining, 272067, China.

出版信息

Biomaterials. 2024 Jul;308:122565. doi: 10.1016/j.biomaterials.2024.122565. Epub 2024 Apr 3.

DOI:10.1016/j.biomaterials.2024.122565
PMID:38603823
Abstract

As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, CuSe@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto CuSe@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus, achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo. Overall, the CuSe@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.

摘要

由于细菌性角膜炎发展迅速,需要及时进行干预。目前的诊断过程耗时且具有侵入性,导致抗生素治疗不当。因此,迫切需要创新的策略来诊断和治疗细菌性角膜炎。在这项研究中,通过将硝基还原酶响应探针(NTRP)负载到 CuSe@BSA 上,开发了 CuSe@BSA@NTRP 纳米粒子。这些纳米粒子表现出了集成荧光成像和抗菌能力。体外和体内实验表明,由于释放的 NTRP 与细菌内源性硝基还原酶(NTR)之间的相互作用,纳米粒子在 30 分钟内产生了响应性的荧光信号。当与低温光热疗法(PTT)结合使用时,纳米粒子有效地消除了大肠杆菌和金黄色葡萄球菌,实现了超过 95%的抗菌功效,并促进了体内角膜伤口部位的再上皮化过程。总的来说,CuSe@BSA@NTRP 纳米粒子有望实现细菌性角膜炎的快速、非侵入性原位诊断、治疗和治疗效果的可视化评估。

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