Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, 3-1-1 Tsushimanaka, Okayama, 700-8530, Japan.
Department of Biomedical Engineering, Faculty of Engineering, Okayama University, 3-1-1 Tsushimanaka, Okayama, 700-8530, Japan.
Sci Rep. 2021 Jul 22;11(1):14936. doi: 10.1038/s41598-021-94249-7.
Methods to spatially induce apoptosis are useful for cancer therapy. To control the induction of apoptosis, methods using light, such as photochemical internalization (PCI), have been developed. We hypothesized that photoinduced delivery of microRNAs (miRNAs) that regulate apoptosis could spatially induce apoptosis. In this study, we identified pre-miR-664a as a novel apoptosis-inducing miRNA via mitochondrial apoptotic pathway. Further, we demonstrated the utility of photoinduced cytosolic dispersion of RNA (PCDR), which is an intracellular RNA delivery method based on PCI. Indeed, apoptosis is spatially regulated by pre-miR-664a and PCDR. In addition, we found that apoptosis induced by pre-miR-664a delivered by PCDR was more rapid than that by lipofection. These results suggest that pre-miR-664a is a nucleic acid drug candidate for cancer therapy and PCDR and pre-miR-664a-based strategies have potential therapeutic uses for diseases affecting various cell types.
空间诱导细胞凋亡的方法可用于癌症治疗。为了控制细胞凋亡的诱导，已经开发了使用光的方法，如光化学内化（PCI）。我们假设通过调控细胞凋亡的微小 RNA（miRNA）的光诱导传递可以实现空间诱导细胞凋亡。在这项研究中，我们通过线粒体凋亡途径鉴定出 pre-miR-664a 是一种新型的凋亡诱导 miRNA。此外，我们还证明了基于 PCI 的细胞溶质中 RNA 分散（PCDR）的有效性，这是一种基于 PCI 的细胞内 RNA 传递方法。实际上，通过 pre-miR-664a 和 PCDR 可以实现空间调节细胞凋亡。此外，我们发现 PCDR 传递的 pre-miR-664a 诱导的细胞凋亡比脂质体转染诱导的细胞凋亡更快。这些结果表明，pre-miR-664a 是一种用于癌症治疗的核酸药物候选物，并且基于 PCDR 和 pre-miR-664a 的策略对于影响各种细胞类型的疾病具有潜在的治疗用途。
