Regio-isomerization Optimization Strategy for Photosensitizers: Achieving Ultrahigh Type I Reactive Oxygen Species Generation to Enhance Cancer Photoimmunotherapy

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-03-13 DOI:10.1021/acs.jmedchem.4c02916

Quan Wang, Lili Yang, Xiaoyu Xing, Wenjie Liang, Renzhi Wu, Chen Xiong, Meng Wu, Cheng Zhong, Haoke Zhang, Shixuan Wang, Fan Xia, Xiaoding Lou, Dugang Chen, Jun Dai

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Abstract

Phototherapy, renowned for its noninvasiveness, is widely employed in tumor treatment. However, the tumor microenvironment is usually hypoxic, with insufficient reactive oxygen species (ROS) production, severely limiting its application. Herein, we introduce a regio-isomerization optimization strategy and have synthesized four regio-isomeric photosensitizers featuring a donor–acceptor (D–A) configuration by tactically varying the linkage sites between D and A. Among them, TAF-3 with excellent photostability has an ultrahigh type I ROS production efficiency (4.79 times that of methylene blue) and a photothermal conversion efficiency of 41.7%. TAF-3 improves the conjugation degree; produces an appropriate intramolecular charge transfer effect, which enhances its optical properties and phototherapeutic efficiency; and promotes a stronger immune cell death effect, reducing postoperative melanoma recurrence by 60%. Overall, the optical attributes of D–A type photosensitizers can be tailored through the precision modulation of regio-isomerization, offering a promising avenue for the advancement of clinical photosensitizers suitable for phototherapy.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.