Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY.
Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
Photochem Photobiol. 2023 Mar;99(2):420-436. doi: 10.1111/php.13726. Epub 2022 Oct 14.
Bladder cancer is the first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here, we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers and better control of light. Non-muscle invasive bladder cancers are more suitable for PDT than muscle invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of non-muscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but was not successful due to low therapeutic efficacy. To enhance the efficacy of PpIX-PDT, we have been working on combining it with singlet oxygen-activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX-PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off-target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an In vivo setting without causing collateral damage to bladder function.
膀胱癌是 PDT 于 1993 年首次获得临床批准的首个癌症。不幸的是，由于膀胱收缩等副作用，该疗法并未成功。在此，我们总结了 PDT 治疗膀胱癌的最新进展，重点介绍了光敏剂和制剂。减少副作用的一般策略是膀胱内给予光敏剂、使用光敏剂的靶向策略以及更好地控制光。与肌层浸润性和转移性膀胱癌相比，非肌层浸润性膀胱癌更适合 PDT 治疗。2010 年，FDA 批准了使用 PpIX 荧光的蓝光膀胱镜检查，用于非肌层浸润性膀胱癌的光动力诊断。HAL 产生的 PpIX 也用于 PDT，但由于疗效低而未成功。为了提高 PpIX-PDT 的疗效，我们一直在研究将其与单重态氧激活前药结合使用。这些前药的使用增加了 PpIX-PDT 的疗效。由于 PpIX 在癌细胞中的优先形成，降低了脱靶毒性，前药也提高了肿瘤的选择性。未来的挑战包括改进前药和穿过膀胱屏障将光递送至更深的肿瘤组织，并在不引起膀胱功能副损伤的情况下在体内环境中产生有效的治疗反应。
