Ultrasound-dependent cytoplasmic internalization of a peptidesonosensitizer conjugate

作者：Inaba Yuki; Watanabe Kazunori; Kitamatsu Mizuki; Nakata Eiji; Harada Atsushi; Ohtsuki Takashi^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(15): 4212-4217.

DOI：10.1016/j.bmc.2017.06.024

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

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 peptidesonosensitizer 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.

• 出版日期2017-8-1