TY - JOUR
T1 - Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate
AU - Inaba, Yuki
AU - Watanabe, Kazunori
AU - Kitamatsu, Mizuki
AU - Nakata, Eiji
AU - Harada, Atsushi
AU - Ohtsuki, Takashi
N1 - Funding Information:
We thank Shota Nagahiro (Okayama University) for help with the revision. This work was supported by JSPS KAKENHI, Japan (No. 25560224 to T. O., A. H., and E. N.), Grants-in-Aid for Scientific Research on Innovative Areas ?Nanomedicine Molecular Science? (26107711 to T. O.), and the ?Joint Usage/Research Program on Zero-Emission Energy Research?, Institute of Advanced Energy, Kyoto University, Japan (ZE28B-32).
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017
Y1 - 2017
N2 - A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells. To promote escape of the entrapped TatBim-RB molecules, cells were irradiated with ultrasound, which successfully induced endosomal escape and cytoplasmic dispersion of TatBim-RB, and subsequently apoptosis. Our results suggest that this peptide-sonosensitizer conjugate strategy may facilitate numerous kinds of medicinal chemistry studies, and furthermore, this specific conjugate may exhibit potential as a novel therapeutic agent for the promotion of apoptosis.
AB - A method to induce cytoplasmic peptide delivery, using ultrasound, was demonstrated using a molecular conjugate of a cell-penetrating peptide (CPP), a functional peptide, and a sonosensitizer. As a model of such molecular conjugates, TatBim-RB, consisting of the Tat CPP, the Bim apoptosis inducing peptide, and the sonosensitizer rose bengal was synthesized. CPPs have been widely used for intracellular delivery of various cargos; however, CPP-fused molecules tend to become entrapped in endosomes, as was observed for TatBim-RB molecules applied to cells. To promote escape of the entrapped TatBim-RB molecules, cells were irradiated with ultrasound, which successfully induced endosomal escape and cytoplasmic dispersion of TatBim-RB, and subsequently apoptosis. Our results suggest that this peptide-sonosensitizer conjugate strategy may facilitate numerous kinds of medicinal chemistry studies, and furthermore, this specific conjugate may exhibit potential as a novel therapeutic agent for the promotion of apoptosis.
KW - Apoptosis
KW - Cell-penetrating peptide
KW - Endosomal escape
KW - Sonosensitizer
KW - Ultrasound
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U2 - 10.1016/j.bmc.2017.06.024
DO - 10.1016/j.bmc.2017.06.024
M3 - Article
C2 - 28647135
AN - SCOPUS:85021106366
VL - 25
SP - 4212
EP - 4217
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 15
ER -