Ding Qihang, Rha Hyeonji, Yoon Changyu, Kim Yujin, Hong So Jin, Kim Hui Ju, Li Yang, Lee Min Hee, Kim Jong Seung
School of Chemical Engineering & Pharmacy, Pharmaceutical Research Institute, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Wuhan Institute of Technology, Wuhan 430205, China; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
J Control Release. 2025 Jun 10;382:113720. doi: 10.1016/j.jconrel.2025.113720. Epub 2025 Apr 12.
Phototherapy, comprising photodynamic therapy (PDT) and photothermal therapy (PTT), was first introduced over a century ago and has since evolved into a versatile cancer treatment modality. While numerous studies have explored regulated cell death (RCD) mechanisms induced by phototherapy, a comprehensive synthesis centered on mitochondria-targeted phototherapeutic strategies and agents as mediators of RCD is still lacking. This review provides a systematic and in-depth analysis of recent advances in mitochondria-centered mechanisms driving phototherapy-induced death pathways, including apoptosis, autophagy, pyroptosis, immunogenic cell death, ferroptosis, and cuproptosis. We highlight the critical role of mitochondria as central regulators of these death pathways in response to phototherapeutic interventions. Moreover, we discuss fundamental design strategies for developing precision-targeted phototherapeutic materials to enhance efficacy and minimize off-target effects. Finally, we identify prevailing challenges and propose future research directions to address these hurdles, paving the way for next-generation mitochondria-targeted phototherapy as a highly effective strategy for cancer management.
光疗法，包括光动力疗法（PDT）和光热疗法（PTT），于一个多世纪前首次被引入，此后已发展成为一种多功能的癌症治疗方式。虽然众多研究探索了光疗法诱导的程序性细胞死亡（RCD）机制，但仍缺乏以线粒体靶向光治疗策略和作为RCD介质的药物为中心的全面综述。本综述对以线粒体为中心驱动光疗法诱导死亡途径的机制的最新进展进行了系统而深入的分析，包括凋亡、自噬、焦亡、免疫原性细胞死亡、铁死亡和铜死亡。我们强调了线粒体作为这些死亡途径响应光治疗干预的核心调节因子的关键作用。此外，我们讨论了开发精准靶向光治疗材料以提高疗效并最小化脱靶效应的基本设计策略。最后，我们确定了当前的挑战并提出了应对这些障碍的未来研究方向，为下一代线粒体靶向光疗法作为一种高效的癌症管理策略铺平道路。
