Photoredox catalysis may be a general mechanism in photodynamic therapy

Mingle Li, Yunjie Xu, Zhongji Pu, Tao Xiong, Haiqiao Huang, Saran Long, Subin Son, Le Yu, Nem Singh, Yunkang Tong, Jonathan L. Sessler, Xiaojun Peng, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Elucidating the underlying photochemical mechanisms of action (MoA) of photodynamic therapy (PDT) may allow its efficacy to be improved and could set the stage for the development of new classes of PDT photosensitizers. Here, we provide evidence that “photoredox catalysis in cells,” wherein key electron transport pathways are disrupted, could constitute a general MoA associated with PDT. Taking the cellular electron donor nicotinamide adenine dinucleotide as an example, we have found that well-known photosensitizers, such as Rose Bengal, BODIPY, phenoselenazinium, phthalocyanine, and porphyrin derivatives, are able to catalyze its conversion to NAD+. This MoA stands in contrast to conventional type I and type II photoactivation mechanisms involving electron and energy transfer, respectively. A newly designed molecular targeting photocatalyst (termed CatER) was designed to test the utility of this mechanism-based approach to photosensitizer development. Photoexcitation of CatER induces cell pyroptosis via the caspase 3/GSDME pathway. Specific epidermal growth factor receptor positive cancer cell recognition, high signal-to-background ratio tumor imaging (SBRTI = 12.2), and good tumor growth inhibition (TGI = 77.1%) are all hallmarks of CatER. CatER thus constitutes an effective near-infrared pyroptotic cell death photo-inducer. We believe the present results will provide the foundation for the synthesis of yet-improved phototherapeutic agents that incorporate photocatalytic chemistry into their molecular design.

Original languageEnglish
Article numbere2210504119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number34
DOIs
Publication statusPublished - 2022 Aug 23

Keywords

  • NADH
  • photodynamic therapy
  • photoredox catalysis
  • pyroptosis

ASJC Scopus subject areas

  • General

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