Faculty of Medicine, University of Tsukuba, Ibaraki 305-8577, Japan.
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.
Int J Mol Sci. 2021 Jul 7;22(14):7306. doi: 10.3390/ijms22147306.
In photodynamic therapy (PDT) for neoplasms, photosensitizers selectively accumulate in cancer tissue. Upon excitation with light of an optimal wavelength, the photosensitizer and surrounding molecules generate reactive oxygen species, resulting in cancer cell-specific cytotoxicity. Porphylipoprotein (PLP) has a porphyrin-based nanostructure. The porphyrin moiety of PLP is quenched because of its structure. When PLP is disrupted, the stacked porphyrins are separated into single molecules and act as photosensitizers. Unless PLP is disrupted, there is no photosensitive disorder in normal tissues. PLP can attenuate the photosensitive disorder compared with other photosensitizers and is ideal for use as a photosensitizer. However, the efficacy of PLP has not yet been evaluated. In this study, the mechanism of cancer cell-specific accumulation of PLP and its cytotoxic effect on cholangiocarcinoma cells were evaluated. The effects were investigated on normal and cancer-like mutant cells. The cytotoxicity effect of PLP PDT in cancer cells was significantly stronger than in normal cells. In addition, reactive oxygen species regulated intracellular PLP accumulation. The cytotoxic effects were also investigated using a cholangiocarcinoma cell line. The cytotoxicity of PLP PDT was significantly higher than that of laserphyrin-based PDT, a conventional type of PDT. PLP PDT could also inhibit tumor growth in vivo.
在肿瘤的光动力疗法（PDT）中，光敏剂选择性地积聚在癌组织中。在最佳波长的光激发下，光敏剂和周围分子会产生活性氧物种，导致癌细胞特异性细胞毒性。卟啉脂蛋白（PLP）具有基于卟啉的纳米结构。由于其结构，PLP 的卟啉部分被猝灭。当 PLP 被破坏时，堆叠的卟啉被分离成单个分子并充当光敏剂。除非 PLP 被破坏，否则正常组织中不会出现光敏性紊乱。PLP 可以减轻光敏性紊乱，与其他光敏剂相比，它是一种理想的光敏剂。然而，PLP 的疗效尚未得到评估。在这项研究中，评估了 PLP 对胆管癌细胞的癌细胞特异性积累机制及其细胞毒性作用。研究了对正常和类似癌细胞突变体的影响。PLP PDT 在癌细胞中的细胞毒性作用明显强于正常细胞。此外，活性氧调节细胞内 PLP 积累。还使用胆管癌细胞系研究了 PLP PDT 的细胞毒性作用。PLP PDT 的细胞毒性明显高于传统的激光卟啉 PDT。PLP PDT 还可以抑制体内肿瘤生长。
