論文

2015年12月

The molecular mechanism of photochemical internalization of cell penetrating peptide-cargophoto-sensitizer conjugates

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

5
開始ページ
18577
終了ページ
18577
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/srep18577
出版者・発行元
NATURE PUBLISHING GROUP

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 O-1(2) molecules from photosensitizers were highly related to the endosomal escape efficiencies. The contribution of O-1(2) was confirmed using O-1(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 O-1(2) lifetime), and that the pH increased in the endosome prior to the endosomal escape of the macromolecule.

Web of Science ® 被引用回数 : 30

リンク情報
DOI
https://doi.org/10.1038/srep18577
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000367075000001&DestApp=WOS_CPL

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