Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8573, Japan.
TAKANO Co. LTD. Miyada-mura, Kamiina-gun, Nagano, 399-4301, Japan.
Commun Biol. 2023 Nov 28;6(1):1212. doi: 10.1038/s42003-023-05598-0.
Polphylipoprotein (PLP) is a recently developed nanoparticle with high biocompatibility and tumor selectivity, and which has demonstrated unprecedentedly high performance photosensitizer in photodynamic therapy (PDT) and photodynamic diagnosis. On the basis of these discoveries, PLP is anticipated to have a very high potential for PDT. However, the mechanism by which PLP kills cancer cells effectively has not been sufficiently clarified. To comprehensively understand the PLP-induced PDT processes, we conduct multifaceted experiments using both normal cells and cancer cells originating from the same sources, namely, RGM1, a rat gastric epithelial cell line, and RGK1, a rat gastric mucosa-derived cancer-like mutant. We reveal that PLP enables highly effective cancer treatment through PDT by employing a unique mechanism that utilizes the process of autophagy. The dynamics of PLP-accumulated phagosomes immediately after light irradiation are found to be completely different between normal cells and cancer cells, and it becomes clear that this difference results in the manifestation of the characteristic effect of PDT when using PLP. Since PLP is originally developed as a drug delivery agent, this study also suggests the potential for intracellular drug delivery processes through PLP-induced autophagy.
多聚赖氨酸(PLP)是一种新型纳米颗粒,具有良好的生物相容性和肿瘤选择性,并在光动力治疗(PDT)和光动力诊断中表现出前所未有的高效光敏剂。基于这些发现,PLP 有望在 PDT 中具有很高的应用潜力。然而,PLP 有效杀死癌细胞的机制尚未得到充分阐明。为了全面了解 PLP 诱导的 PDT 过程,我们使用源自同一来源的正常细胞和癌细胞(即大鼠胃上皮细胞系 RGM1 和大鼠胃黏膜衍生的癌样突变体 RGK1)进行了多方面的实验。我们揭示了 PLP 通过利用自噬过程的独特机制,通过 PDT 实现了高效的癌症治疗。在光照射后立即发现 PLP 聚集的吞噬体的动力学在正常细胞和癌细胞之间完全不同,并且很明显,当使用 PLP 时,这种差异导致了 PDT 的特征效应的表现。由于 PLP 最初被开发为药物递送剂,因此本研究还表明通过 PLP 诱导的自噬进行细胞内药物递送过程的潜力。