Tao Jiawen, Yuan Zhifei, Zhou Mengjiao
The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, China.
School of Pharmacy, Nantong University, Nantong, China.
Front Pharmacol. 2025 Aug 25;16:1667812. doi: 10.3389/fphar.2025.1667812. eCollection 2025.
Photodynamic therapy (PDT) induces cancer cell death by utilizing photosensitizers to generate reactive oxygen species (ROS) upon light irradiation, which in turn trigger oxidative stress. However, the therapeutic efficacy of PDT is constrained by the short lifetimes and limited diffusion range of ROS, resulting in suboptimal outcomes and off-target effects. Specific organelle targeting, facilitated by rationally engineered photosensitizers and nanoplatforms with precise drug delivery capabilities that activate organelle-mediated cell death pathways, can maximize localized oxidative damage, enhance therapeutic efficacy, and minimize systemic toxicity. This review synthesizes advancements in organelle-targeted PDT, focusing on critical subcellular compartments (, mitochondria, lysosomes, nuclei, cell membranes, ribosome, endoplasmic reticulum, golgi apparatus, autophagosome). It systematically summarizes the structural characteristics, design strategies, targeting mechanisms, and therapeutic effects of these organelle-targeted systems, with particular emphasis on organelle-mediated cell death signaling pathways. Ultimately, current challenges, prospective opportunities, and future research directions in organelle targeting are delineated, providing a strategic framework to advance organelle-targeted PDT toward precision therapy.
光动力疗法（PDT）通过利用光敏剂在光照下产生活性氧（ROS）来诱导癌细胞死亡，进而引发氧化应激。然而，PDT的治疗效果受到ROS短寿命和有限扩散范围的限制，导致治疗效果欠佳和脱靶效应。通过合理设计的光敏剂和具有精确药物递送能力的纳米平台来实现特定细胞器靶向，这些平台可激活细胞器介导的细胞死亡途径，从而最大化局部氧化损伤、提高治疗效果并最小化全身毒性。本综述综合了细胞器靶向光动力疗法的进展，重点关注关键的亚细胞区室（线粒体、溶酶体、细胞核、细胞膜、核糖体、内质网、高尔基体、自噬体）。系统总结了这些细胞器靶向系统的结构特征、设计策略、靶向机制和治疗效果，特别强调了细胞器介导的细胞死亡信号通路。最终，阐述了细胞器靶向目前面临的挑战、潜在机遇和未来研究方向，为推动细胞器靶向光动力疗法向精准治疗发展提供了战略框架。
