Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA.
Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Photochem Photobiol. 2024 Nov-Dec;100(6):1659-1675. doi: 10.1111/php.13933. Epub 2024 Mar 27.
It has been 30 years since Photofrin-PDT was approved for the treatment of bladder cancer in Canada. However, Photofrin-PDT failed to gain popularity due to bladder complications. The PDT with red light and IV-administered Photofrin could permanently damage the bladder muscle. We have been developing a new combination strategy of PpIX-PDT with singlet oxygen-cleavable prodrugs for NMIBC with minimal side effects, avoiding damage to the bladder muscle layer. PpIX can be excited by either green (532 nm) or red (635 nm) light. Red light could be more efficacious in vivo due to its deeper tissue penetration than green light. Since HAL preferentially produces PpIX in tumors, we hypothesized that illuminating PpIX with red light might spare the muscle layer. PpIX-PDT was used to compare green and red laser efficacy in vitro and in vivo. The IC of in vitro PpIX-PDT was 18 mW/cm with the red laser and 22 mW/cm with the green laser. The in vivo efficacy of the red laser with 50, 75, and 100 mW total dose was similar to the same dose of green laser in reducing tumor volume. Combining PpIX-PDT with prodrugs methyl-linked mitomycin C (Mt-L-MMC) and rhodamine-linked SN-38 (Rh-L-SN-38) significantly improved efficacy (tumor volume comparison). PpIX-PDT or PpIX-PDT + prodrug combination did not cause muscle damage in histological analysis. Overall, a combination of PpIX-PDT and prodrug with 635 nm laser is promising for non-muscle invasive bladder cancer treatment.
自 Photofrin-PDT 在加拿大被批准用于膀胱癌治疗以来，已经过去了 30 年。然而，由于膀胱并发症，Photofrin-PDT 并未普及。使用红光和静脉注射 Photofrin 的 PDT 会永久性地损伤膀胱肌肉。我们一直在开发一种新的组合策略，即使用卟啉啉-PDT 与单重态氧可裂解前药联合治疗非肌肉浸润性膀胱癌，以最小的副作用避免膀胱肌肉层损伤。PpIX 可以被绿光（532nm）或红光（635nm）激发。由于红光的组织穿透深度比绿光更深，因此在体内可能更有效。由于 HAL 优先在肿瘤中产生 PpIX，我们假设用红光照射 PpIX 可能会使肌肉层免受损伤。我们使用 PpIX-PDT 比较了体外和体内的绿光和红光激光疗效。体外 PpIX-PDT 的 IC 为 18mW/cm 时用红光，22mW/cm 时用绿光。50、75 和 100mW 总剂量的红光激光的体内疗效与相同剂量的绿光激光在减少肿瘤体积方面相似。将 PpIX-PDT 与前药甲基连接丝裂霉素 C（Mt-L-MMC）和罗丹明连接 SN-38（Rh-L-SN-38）联合使用可显著提高疗效（肿瘤体积比较）。在组织学分析中，PpIX-PDT 或 PpIX-PDT+前药联合治疗均未引起肌肉损伤。总的来说，635nm 激光联合 PpIX-PDT 和前药治疗非肌肉浸润性膀胱癌具有广阔的前景。
