The molecular mechanism of photochemical internalization of cell penetrating peptide-cargo-photosensitizer conjugates

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number18577
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Dec 21 2015

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Cell-Penetrating Peptides
Photosensitizing Agents
Coloring Agents
Time-Lapse Imaging
Endosomes
Optical Imaging
Cytosol
Nucleic Acids
Light
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • General

Cite this

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.

In: Scientific Reports, Vol. 5, 18577, 21.12.2015.

Research output: Contribution to journalArticle

Ohtsuki, Takashi ; Miki, Shunya ; Kobayashi, Shouhei ; Haraguchi, Tokuko ; Nakata, Eiji ; Hirakawa, Kazutaka ; Sumita, Kensuke ; Watanabe, Kazunori ; Okazaki, Shigetoshi. / The molecular mechanism of photochemical internalization of cell penetrating peptide-cargo-photosensitizer conjugates. In: Scientific Reports. 2015 ; Vol. 5.
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