Effect of an Endothelin B Receptor Agonist on the Tumor Accumulation of Nanocarriers

Haitao Feng; Le Thanh Nam; Takuma Yoshikawa; Akihiro Kishimura; Takeshi Mori; Yoshiki Katayama

doi:10.1248/bpb.b20-00367

Communication to the Editor

Effect of an Endothelin B Receptor Agonist on the Tumor Accumulation of Nanocarriers

Haitao Feng, Le Thanh Nam, Takuma Yoshikawa, Akihiro Kishimura, Takeshi Mori , Yoshiki Katayama

Author information

Haitao Feng
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
Le Thanh Nam
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
Takuma Yoshikawa
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
Akihiro Kishimura
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
Graduate School of System Life Science, Kyushu University
International Research Center for Molecular Systems, Kyushu University
Takeshi Mori Corresponding author
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
Graduate School of System Life Science, Kyushu University
Yoshiki Katayama
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
Graduate School of System Life Science, Kyushu University
International Research Center for Molecular Systems, Kyushu University
Center for Advanced Medical Innovation, Kyushu University
Department of Biomedical Engineering, Chung Yuan Christian University

Keywords: enhanced permeability and retention effect, endothelin B receptor, liposome, tumor accumulation

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Supplementary material

2020 Volume 43 Issue 9 Pages 1301-1305

DOI https://doi.org/10.1248/bpb.b20-00367

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Abstract

Enhancing blood flow to tumors is a prominent strategy for improving the tumor accumulation of macromolecular drugs through the enhanced permeability and retention (EPR) effect. IRL-1620 is an agonist of the endothelin B receptor, and is a promising molecule to enhance tumor blood flow by activating endothelial nitric oxide synthase. However, contradictory effects on tumor blood flow modulation have been reported because the effects of IRL-1620 may differ in different animal models. Here, we examined for the first time the effect of IRL-1620 on the EPR effect for PEGylated liposomes in a CT-26 murine colon cancer model. Co-injection of IRL-1620 at an optimum dose (3 nmol/kg) nearly doubled the tumor accumulation of liposomes compared with controls, indicating that IRL-1620 enhanced the EPR effect in the present colon cancer model. Co-injection of IRL-1620 is a promising strategy to improve the therapeutic effects of macromolecular drugs while reducing their side effects.

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