An ER-targeted, Viscosity-sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway.

Autor: Zeng S; State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China.; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Wang Y; State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Chen C; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Kim H; Department of Chemistry and Nanoscience, Ewha Womans University, 03760, Seoul, Korea., Liu X; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Jiang M; State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Yu Y; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Kafuti YS; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Chen Q; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Wang J; State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China.; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Peng X; State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China., Li H; State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China.; MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, 2 Linggong Road, Hi-tech Zone, 116024, Dalian, China.; Provincial Key Laboratory of Interdisciplinary Medical Engineering for Gastrointestinal Carcinoma, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute), 110042, Shenyang, Liaoning, China., Yoon J; Department of Chemistry and Nanoscience, Ewha Womans University, 03760, Seoul, Korea.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Feb 26; Vol. 63 (9), pp. e202316487. Date of Electronic Publication: 2024 Jan 24.
DOI: 10.1002/anie.202316487
Abstrakt: The concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER-ZS for endoplasmic reticulum (ER)-targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER-targeted functional groups (p-toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER-ZS demonstrated substantial fluorescence turn-on only after binding to the ER, independent of other physiological environments. In addition, ER-ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER-ZS is a type I photosensitizer, producing O 2 ⋅ - and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O 2 ) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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