A lysosome-targetable two-photon excited near-infrared fluorescent probe for visualizing hypochlorous acid-involved arthritis and its treatment

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作者
Mao, Guo-Jiang [1 ]
Wang, Ying-Ying [1 ]
Dong, Wen-Pei [1 ]
Meng, Hong-Min [2 ]
Wang, Qian-Qian [3 ]
Luo, Xiao-Feng [4 ]
Li, Yao [1 ]
Zhang, Guisheng [1 ]
机构
[1] Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Che
[2] College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou,450052, China
[3] Department of Pharmacy, Xinxiang Medical University, 601 Jinsui Road, Xinxiang,453003, China
[4] Gansu Chemical Industry Research Institute CO., LTD., Gansu Key Laboratory of Fine Chemicals, 1 Guchengping, Chengguan District, Lanzhou,730020, China
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摘要
Lysosome of phagocyte is the main site of hypochlorous acid (HClO) production, and HClO can be employed as the biomarker for the diagnosis and treatment evaluation of arthritis. In recent years, developing fluorescent probes for lysosomal HClO has attracted considerable attention, but most of them still have some defects, such as autofluorescence, phototoxicity and photobleaching because of their excitation and emission located in short-wavelength region. Due to the advantages of two-photon fluorescent probes with near-infrared emissions, a lysosome-targetable two-photon fluorescent probe (Lyso-TP-HClO) with a near-infrared emission was reported in this paper. Lyso-TP-HClO has a high selectivity and a high sensitivity to HClO in the linear range (10.0 × 10−8 to 5.0 × 10−6 M), with a detection limit of 3.0 × 10−8 M. Due to the two-photon excited near-infrared emission, Lyso-TP-HClO has excellent imaging performances, such as small autofluorescence, excellent photostability, and large imaging depth. Furthermore, Lyso-TP-HClO was successfully employed for visualizing lysosomal HClO in bacteria-infected cells. At last, we have successfully used Lyso-TP-HClO to image the arthritis and evaluate the treatment of arthritis in mice. All the results confirm that Lyso-TP-HClO is a useful chemical tool for imaging of lysosomal HClO, the diagnosis of arthritis, and treatment evaluation of arthritis. © 2020 Elsevier B.V.
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