Azad Abul Kalam, Dinakaran Deepak, Moore Ronald B
Department of Oncology, University of Alberta, 11560 University Ave, Edmonton, AB, T6G 1Z2, Canada.
Department of Medical Biophysics, University of Toronto, Temerty Faculty of Medicine, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Sci Rep. 2025 Aug 11;15(1):29299. doi: 10.1038/s41598-025-14652-2.
Photodynamic therapy (PDT) represents a promising cancer treatment strategy, leveraging external light sources to activate photosensitizers, which in turn generate reactive oxygen species (ROS) to target and destroy tumor cells. However, PDT's efficacy has traditionally been limited to surface tumors due to limited light penetration through deep tissue structures requiring complex fiber optic delivery. Recent advancements have introduced nanoscintillators as an internal light source for photosensitizers, triggered by targeted X-ray radiation, thus extending the applicability of PDT to deep-seated tumors. While the in vitro tumor cell killing mechanisms of PDT have been extensively documented, comprehensive in vivo studies elucidating the mechanisms underlying radiation-activated photodynamic therapy (radioPDT) remain limited. In this study, we demonstrated that protoporphyrin IX-based radioPDT augments ROS generation, leading to PC3 prostate tumor cell killing in vivo, impeding tumor growth. ROS production led to a reduction in tumor vascular density with corresponding intratumoral hypoxia, while tumor vascular maturity remained unaffected. These results shed light on the multifaceted effects of radioPDT on the tumor microenvironment, emphasizing the potential for synergistic radiotherapeutic strategies in cancer treatment.
光动力疗法（PDT）是一种很有前景的癌症治疗策略，它利用外部光源激活光敏剂，进而产生活性氧（ROS）来靶向并破坏肿瘤细胞。然而，由于光穿透深层组织结构的能力有限，需要复杂的光纤传输，传统上PDT的疗效仅限于浅表肿瘤。最近的进展引入了纳米闪烁体作为光敏剂的内部光源，由靶向X射线辐射触发，从而将PDT的适用性扩展到深部肿瘤。虽然PDT在体外肿瘤细胞杀伤机制方面已有大量文献记载，但阐明辐射激活光动力疗法（radioPDT）潜在机制的全面体内研究仍然有限。在本研究中，我们证明基于原卟啉IX的radioPDT可增强ROS生成，导致体内PC3前列腺肿瘤细胞死亡，抑制肿瘤生长。ROS的产生导致肿瘤血管密度降低，同时肿瘤内出现缺氧，而肿瘤血管成熟度未受影响。这些结果揭示了radioPDT对肿瘤微环境的多方面影响，强调了其在癌症治疗中协同放射治疗策略的潜力。
