TY - JOUR
T1 - Effect of an Endothelin B Receptor Agonist on the Tumor Accumulation of Nanocarriers
AU - Feng, Haitao
AU - Nam, Le Thanh
AU - Yoshikawa, Takuma
AU - Kishimura, Akihiro
AU - Mori, Takeshi
AU - Katayama, Yoshiki
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Challenging Research (project No. 18K19148) of MEXT, Japan.
Publisher Copyright:
© 2020 The Pharmaceutical Society of Japan
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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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U2 - 10.1248/bpb.b20-00367
DO - 10.1248/bpb.b20-00367
M3 - Article
C2 - 32879203
AN - SCOPUS:85090261923
SN - 0918-6158
VL - 43
SP - 1301
EP - 1305
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 9
ER -
