Here we present examples of photoresponsive molecules that photo-dependently enter the cytoplasm based on the principle of photochemical internalization, and how they have been developed and used. The photoresponsive molecules discussed here are complex molecules consisting of a photosensitizer, a cell-penetrating peptide, and a cargo molecule (molecule to be delivered into the cytoplasm). When administered to cells, this photoresponsive molecule enters the cell by endocytosis and becomes trapped within endosomes, but when exposed to light, it escapes the endosomes and functions in the cytoplasm. Examples of these molecules include photoresponsive RNA carriers [1, 2] and photoresponsive apoptosis-inducing molecules [3]. Among them, we report a method (Photoinduced Cytosolic Dispersion of RNA (PCDR) method) for cytosolic delivery of small RNA molecules such as short hairpin RNA (shRNA) and microRNA (miRNA) using the photoresponsive RNA carrier. Specifically, we present the mechanism of PCDR [4, 5], RNA transfection triggered by light of different wavelengths [6], and spatio-temporally photo-triggered RNAi [7]. In addition, we report on the analysis of cellular functions by photoresponsive complex molecules [8] and discuss their potential for medical applications [9].
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[8] Kim, H., Watanabe, S., Kitamatsu, M., Watanabe, K., Ohtsuki, T., Sci. Rep. 10, 19087 (2020)
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