Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate

Yuki Inaba, Kazunori Watanabe, Mizuki Kitamatsu, Eiji Nakata, Atsushi Harada, Takashi Ohtsuki

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4212-4217
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number15
DOIs
Publication statusPublished - Aug 1 2017

Fingerprint

Cell-Penetrating Peptides
Ultrasonics
Peptides
Apoptosis
Molecules
Rose Bengal
Molecular Models
Pharmaceutical Chemistry
Endosomes
Therapeutics

Keywords

  • Apoptosis
  • Cell-penetrating peptide
  • Endosomal escape
  • Sonosensitizer
  • Ultrasound

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate. / Inaba, Yuki; Watanabe, Kazunori; Kitamatsu, Mizuki; Nakata, Eiji; Harada, Atsushi; Ohtsuki, Takashi.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 15, 01.08.2017, p. 4212-4217.

Research output: Contribution to journalArticle

Inaba, Yuki ; Watanabe, Kazunori ; Kitamatsu, Mizuki ; Nakata, Eiji ; Harada, Atsushi ; Ohtsuki, Takashi. / Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate. In: Bioorganic and Medicinal Chemistry. 2017 ; Vol. 25, No. 15. pp. 4212-4217.
@article{fa84269c6ddb4d939e008ee7027a7276,
title = "Ultrasound-dependent cytoplasmic internalization of a peptide-sonosensitizer conjugate",
abstract = "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.",
keywords = "Apoptosis, Cell-penetrating peptide, Endosomal escape, Sonosensitizer, Ultrasound",
author = "Yuki Inaba and Kazunori Watanabe and Mizuki Kitamatsu and Eiji Nakata and Atsushi Harada and Takashi Ohtsuki",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.bmc.2017.06.024",
language = "English",
volume = "25",
pages = "4212--4217",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "15",

}

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

PY - 2017/8/1

Y1 - 2017/8/1

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

UR - http://www.scopus.com/inward/record.url?scp=85021106366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021106366&partnerID=8YFLogxK

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 -