Regio-isomerization Optimization Strategy for Photosensitizers: Achieving Ultrahigh Type I Reactive Oxygen Species Generation to Enhance Cancer Photoimmunotherapy
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.
Authors
- Dugang Chen (ORCID: https://orcid.org/0000-0003-2653-1232)
- Lili Yang (ORCID: https://orcid.org/0000-0001-6568-0404)
- Wenjie Liang (ORCID: https://orcid.org/0000-0003-2947-2901)
- Xiaoding Lou (ORCID: https://orcid.org/0000-0002-6556-2034)
- Haoke Zhang (ORCID: https://orcid.org/0000-0001-7309-2506)
- Renzhi Wu (ORCID: https://orcid.org/0000-0001-8991-2417)
- Fan Xia (ORCID: https://orcid.org/0000-0001-7705-4638)
- Xiaoyu Xing (ORCID: https://orcid.org/0000-0003-0539-0936)
- Quan Wang (ORCID: https://orcid.org/0000-0002-5021-7238)
- Xiong Chen (ORCID: https://orcid.org/0000-0001-5316-6512)
- Meng Wu (ORCID: https://orcid.org/0000-0001-8822-4700)
- Jun Yan Dai (ORCID: https://orcid.org/0009-0003-8751-410X)
- Cheng Zhong (ORCID: https://orcid.org/0000-0002-7756-9313)
- Shixuan Wang
Institutions
- China University of Geosciences (CN)
- Wuhan University (CN)
- National Clinical Research (US)
- Tongji Hospital (CN)
- Huazhong University of Science and Technology (CN)
- Zhejiang University (CN)
- Wuhan Institute of Technology (CN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-03-13
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c02916
- Citations
- 4
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 2.70
Funders
- Natural Science Foundation of Shenzhen City
- National Natural Science Foundation of China
- Natural Science Foundation of Hubei Province
- Israel Science Foundation
- National Key Research and Development Program of China