学術雑誌論文 The molecular mechanism of photochemical internalization of cell penetrating peptide-cargo-photosensitizer conjugates.

Ohtsuki, Takashi  ,  Miki, Shunya  ,  Kobayashi, Shouhei  ,  Haraguchi, Tokuko  ,  Nakata, Eiji  ,  Hirakawa, Kazutaka  ,  Sumita, Kensuke  ,  Watanabe, Kazunori  ,  Okazaki, Shigetoshi

52015-12-21 , Nature Publishing Group
ISSN:2045-2322
内容記述
In many drug delivery strategies, an inefficient transfer of macromolecules such as proteins and nucleic acids to the cytosol often occurs because of their endosomal entrapment. One of the methods to overcome this problem is photochemical internalization, which is achieved using a photosensitizer and light to facilitate the endosomal escape of the macromolecule. In this study, we examined the molecular mechanism of photochemical internalization of cell penetrating peptide-cargo (macromolecule)-photosensitizer conjugates. We measured the photophysical properties of eight dyes (photosensitizer candidates) and determined the respective endosomal escape efficiencies using these dyes. Correlation plots between these factors indicated that the photogenerated [1]O[2] molecules from photosensitizers were highly related to the endosomal escape efficiencies. The contribution of [1]O[2] was confirmed using [1]O[2] quenchers. In addition, time-lapse fluorescence imaging showed that the photoinduced endosomal escape occurred at a few seconds to a few minutes after irradiation (much longer than [1]O[2] lifetime), and that the pH increased in the endosome prior to the endosomal escape of the macromolecule.
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http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/216044/1/srep18577.pdf

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