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

我们研究了光动力疗法（PDT）和声动力疗法（SDT）的组合，以提高在可移植的小鼠鳞状细胞癌（SCC）模型的杀瘤效果。使用了两种致敏剂：新开发的光敏剂脱镁黄药衍生物PH-1126和常用的声敏剂镓卟啉类似物ATX-70。以5或10 mg/kg.bw的剂量对小鼠i. p.注射PH-1126或ATX-70。24小时（ATX-70）或36小时（PH-1126）注射后，SCC接受激光照射（肿瘤中最佳药物浓度的时间），（ATX-70为88 J/cm 2，575 nm; 44 J/cm 2，650 nm）（PDT）、超声辐照（0.51 W/cm 2，1.0 MHz，10分钟）（SDT）或两种处理的组合。使用PH-1126或ATX-70作为敏化剂的PDT和SDT的组合导致与任一单一治疗（27-77%）相比显著改善的肿瘤生长抑制（92-98%）（累加效应）。使用PH-1126的组合在治疗后20天实现了25%的治疗小鼠无肿瘤。此外，PDT+ SDT治疗的小鼠的中位存活期（从照射到死亡）（>120天）显著大于单次治疗组（77-95天）。组织学变化显示，联合治疗可诱导肿瘤坏死比任何单一方式深2-3倍。PDT和SDT的联合应用将对非浅表性或结节性肿瘤的治疗非常有用。

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.