Martinez de Pinillos Bayona Alejandra, Woodhams Josephine H, Pye Hayley, Hamoudi Rifat A, Moore Caroline M, MacRobert Alexander J
Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.
Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.
Cancer Lett. 2017 May 1;393:68-75. doi: 10.1016/j.canlet.2017.02.018. Epub 2017 Feb 20.
This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS and TPPS) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS and TPCS were shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer.
本研究表明，光化学内化（PCI）在体外前列腺癌治疗中的效果优于光动力疗法（PDT），并且在临床上可以改善前列腺癌的光动力疗法，同时避免化疗的副作用。此外，该研究使用标准的二维单层培养和三维仿生模型，评估了两种不同光敏剂（TPCS和TPPS）在前列腺癌细胞（人PC3和大鼠MatLyLu）中进行光化学内化的潜力。光敏剂单独用于光动力疗法（PDT）或与细胞毒素皂草素联合使用（PCI）。结果显示，在光照处理前，TPPS和TPCS定位于离散的细胞质囊泡中，光照激发后重新分布到细胞质中。两种光敏剂在PC3细胞中的摄取量均高于MatLyLu细胞。在二维模型中，PCI在两种细胞系中导致的细胞死亡均比单独的PDT更多。在三维模型中，也观察到了形态学变化。基于皂草素的毒性在PC3细胞中可忽略不计，但在MatLyLu细胞中较为明显（IC50 = 18 nM）。总之，该研究表明，肿瘤特征如肿瘤细胞生长速率或与药物的相互作用决定了转移性前列腺癌最佳光化学治疗的条件。
