한빛사논문
- 조회276
Mingle Lia,1, Yunjie Xua,1, Zhongji Pub, Tao Xiongc, Haiqiao Huangc, Saran Longc, Subin Sona, LeYua, Nem Singha, Yunkang Tongc, Jonathan L. Sesslerd,2, Xiaojun Pengc,2, and Jong Seung Kima,2
aDepartment of Chemistry, Korea University, Seoul 02841, Korea; bHangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China; cState Key Laboratory of Fine Chemicals, Dalian University ofTechnology, Dalian 116024, China; and dDepartment of Chemistry, University of Texasat Austin, Austin, TX 78712-1224
1M.L. and Y.X. contributed equally to this work.
2To whom correspondence may be addressed: Jonathan L. Sessler, Xiaojun Peng, Jong Seung Kim
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.
논문정보
- Research article
- 2022년 08월 (BRIC 등록일 2022-11-29)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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