Effect of photodynamic therapy on experimental skin squamous cell carcinoma using a newly developed photosensitizer

我们在可移植小鼠鳞状细胞癌（SCC）模型中研究了光动力疗法（PDT）和声动力疗法（SDT）联合治疗对肿瘤杀伤效果的改善。使用了两种增敏剂：一种是新开发的光敏剂酚醛衍生物PH-1126，另一种是卟啉镓类似物ATX-70，一种常用的声敏剂。小鼠分别以5或10 mg/kg.bw的剂量注射PH-1126或ATX-70。在注射后24小时（ATX-70）或36小时（PH-1126）（肿瘤中最佳药物浓度时间），SCCs进行激光照射（ATX-70为88 J/cm2, 575 nm； PH-1126为44 J/cm2, 650 nm） （PDT）、超声照射（0.51 W/cm2, 1.0 MHz， 10分钟）（SDT）或两种治疗的组合。PDT和SDT联合使用PH-1126或ATX-70作为增敏剂，与单一治疗（27-77%）相比，显著提高了肿瘤生长的抑制（92-98%）（加性效应）。使用PH-1126的组合在治疗后20天达到25%的治疗小鼠无肿瘤。此外，PDT+ sdt治疗小鼠的中位生存期（从照射到死亡）（>120天）显著大于单一治疗组（77-95天）。组织学变化显示，联合治疗可诱导肿瘤坏死深度为任何单一治疗方式的2-3倍。PDT和SDT联合治疗对于非浅表性或结节性肿瘤非常有用。

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheoforbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at a dose of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44 J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT) or a combination of the two treatments. the combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in a significantly improved inhibition of tumor growth (92-98%) (additive effect) compared to either single treatment (27-77%). The combination using PH-1126 achieved 25% of the treated mice being tumor free at 20 days after treatments. Moreover, the median survival period (from irradiation to death) of PDT+SDT-treated mice (>120 days) was significantly greater than in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times deeper than in any of the single modalities. The combination of PDT and SDT will be very useful for treatment of non-superficial or nodular tumors.