期刊
BIOMATERIALS
卷 286, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121577
关键词
Aggregation-induced emission; Antibacterial; Anti-inflammatory; Nanomaterials; Photodynamic therapy; Upconversion nanoparticles
资金
- National Natural Science Foundation of China [31771026, 32000993, 21871108]
- Zhejiang Provincial Natu-ral Science Foundation of China [LR21H180001]
- Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China [LHDMZ22H300007]
- Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province [WIUCASK19005]
- Zhejiang Traditional Chinese Medicine Scientific Research Fund Project [2021ZA091]
- Wenzhou key program of scientific and technological innovation [ZY2019017]
- Science & Technology program of Wenzhou [Y2020203]
- Project of State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University [J02-20190203]
We designed a multifunctional near-infrared light-responsive nanoplatform for efficient treatment of refractory keratitis. This platform integrates bacteria targeting photodynamic therapy, nitric oxide sterilization, and NO-mediated anti-inflammatory property, showing excellent antibacterial and anti-inflammatory effects.
Stubborn resistant bacteria, bacterial biofilms and severe inflammation are challenging issues in refractory keratitis treatment. Herein, we design a multifunctional near-infrared light-responsive nanoplatform for efficient therapy of refractory keratitis based on a three-birds-with-one-stone strategy, which integrates the bacteria targeting photodynamic therapy, nitric oxide (NO) sterilization, and NO-mediated anti-inflammatory property into one system. This nanoplatform (UCNANs) is constructed using the dual-emissive upconversion nanoparticles (UCNPs) as cores coated with mesoporous silica for the loading of photosensitizers with aggregation-induced emission (AIE) property and the grafting of NO donors and bacteria targeting molecules. Upon irradiation of 808 nm light, UCNPs simultaneously produce UV emission and visible emission to trigger NO release and reactive oxygen species (ROS) such as superoxide radical ( O-2(.-)) generation. Furthermore, O-2(.) resulting from PDT can react with NO to yield powerful oxidizing and nitrating agent peroxynitrite (ONOO-). The three components work synergistically to enhance the antibacterial outcome confirmed by in vitro and in vivo tests. The short-distance light excitation and excitation light absorption are important reasons for reducing the toxicity of ma-terials, especially ultraviolet light damage. Moreover, bacteria elimination reduced endotoxin secretion and the released NO simultaneously inhibit the NF-xB pathways by regulating the expression of toll-like receptor 2 (TRL2) and tumor necrosis factor-alpha (TNF-alpha), which significantly relieves the inflammation of cornea. Given its excellent antibacterial and anti-inflammatory properties, UCNANs provides a competitive strategy for refractory keratitis therapy.
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