Graduate School of Frontier Biosciences, Osaka University, 2-1 Yamadaoka (A1-411), Suita, Osaka, 565-0871, Japan.
Institute of Academic Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka, 565-0871, Japan; Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Photodiagnosis Photodyn Ther. 2017 Dec;20:238-245. doi: 10.1016/j.pdpdt.2017.10.017. Epub 2017 Nov 4.
Subcellular localization of a photosensitizer is known to determine the therapeutic efficacy of photodynamic therapy (PDT). Cell membrane is an optimal target that promises an effective treatment outcome.
We previously developed a novel photosensitizer named porphyrus envelope (PE) by combining hemagglutinating virus of Japan envelope (HVJ-E) with lipidated protoporphyrin IX (PpIX lipid). In the current study, the cellular localization of PE and its ability to induce multiple anti-tumor effect were characterized.
The localization and uptake of PpIX lipid in cells were evaluated with confocal laser scanning microscopy and a cell-based fluorescent assay, respectively. The ability of PE to suppress the migration and proliferation of cancer cells was assessed using a scratch-wound assay. The synergistic effect of PDT and HVJ-E treatment was evaluated using an in vitro experiment with PC-3 cells.
PE localized along the cell membrane and PpIX lipid accumulated selectively in the prostate cancer cells within 10min. Also, PE maintained the ability to undergo fusion and induce cancer cell death even after light irradiation at the dose for PDT. Incubation with PE resulted in delayed migratory and proliferative activity of PC-3 cells. PE-mediated PDT was twice as effective when cells were further incubated with PE following PDT.
PE allows rapid drug delivery targeting the cell membrane. Because the cytotoxicity of HVJ-E was maintained, synergistic effect of HVJ-E and the photochemical reactions resulted in highly effective killing of prostate cancer cells in vitro and thus represents a promising treatment for prostate cancer.
已证实，光敏剂的亚细胞定位决定光动力疗法（PDT）的治疗效果。细胞膜是一种理想的靶向部位，有望带来有效的治疗效果。
我们之前通过将血凝性日本病毒包膜（HVJ-E）与脂化原卟啉 IX（PpIX 脂质）结合，开发了一种名为卟啉包膜（PE）的新型光敏剂。在本研究中，我们对 PE 的细胞定位及其诱导多种抗肿瘤作用的能力进行了表征。
通过共聚焦激光扫描显微镜和基于细胞的荧光测定法分别评估 PpIX 脂质在细胞内的定位和摄取。采用划痕实验评估 PE 抑制癌细胞迁移和增殖的能力。采用体外 PC-3 细胞实验评估 PDT 和 HVJ-E 联合治疗的协同作用。
PE 定位于细胞膜上，PpIX 脂质在 10min 内选择性地积聚在前列腺癌细胞内。此外，PE 即使在 PDT 的光剂量下进行照射后仍能保持融合能力并诱导癌细胞死亡。PE 孵育可延迟 PC-3 细胞的迁移和增殖活性。PE 介导的 PDT 后进一步用 PE 孵育，可使 PDT 的效果提高一倍。
PE 可实现针对细胞膜的快速药物递送。由于 HVJ-E 的细胞毒性得以维持，因此 HVJ-E 和光化学反应的协同作用导致体外前列腺癌细胞的杀伤效果显著增强，因此有望成为前列腺癌的一种治疗方法。
