Systemic Delivery of Small Interfering RNA by Use of Targeted Polycation Liposomes for Cancer Therapy

Eriya Kenjo; Tomohiro Asai; Norihito Yonenaga; Hidenori Ando; Takayuki Ishii; Kentaro Hatanaka; Kosuke Shimizu; Yugo Urita; Takehisa Dewa; Mamoru Nango; Hideo Tsukada; Naoto Oku

doi:10.1248/bpb.b12-00817

Regular Articles

Systemic Delivery of Small Interfering RNA by Use of Targeted Polycation Liposomes for Cancer Therapy

Eriya Kenjo, Tomohiro Asai, Norihito Yonenaga, Hidenori Ando, Takayuki Ishii, Kentaro Hatanaka, Kosuke Shimizu, Yugo Urita, Takehisa Dewa, Mamoru Nango, Hideo Tsukada, Naoto Oku

Author information

Eriya Kenjo
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Tomohiro Asai
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Norihito Yonenaga
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Hidenori Ando
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Takayuki Ishii
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Kentaro Hatanaka
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Kosuke Shimizu
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka
Yugo Urita
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology
Takehisa Dewa
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology
Mamoru Nango
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology
Hideo Tsukada
PET Center, Central Research Laboratory, Hamamatsu Photonics K.K.
Naoto Oku
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka

Keywords: small interfering RNA, liposome, polycation, cancer therapy, positron emission tomography

JOURNAL FREE ACCESS

2013 Volume 36 Issue 2 Pages 287-291

DOI https://doi.org/10.1248/bpb.b12-00817

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Abstract

Novel polycation liposomes decorated with cyclic(Cys-Arg-Gly-Asp-D-Phe) peptide (cyclicRGD)-polyethylene glycol (PEG) (RGD-PEG-polycation liposomes (PCL)) were previously developed for cancer therapy based on RNA interference. Here, we demonstrate the in vivo delivery of small interfering RNA (siRNA) to tumors by use of RGD-PEG-PCL in B16F10 melanoma-bearing mice. Pharmacokinetic data obtained by positron emission tomography showed that cholesterol-conjugated siRNA formulated in RGD-PEG-PCL markedly accumulated in the tumors. Delivered by RGD-PEG-PCL, a therapeutic cocktail of siRNAs composed of cholesterol-conjugated siRNAs for c-myc, MDM2, and vascular endothelial growth factor (VEGF) were able to significantly inhibit the growth of B16F10 melanoma both in vitro and in vivo. These data suggest that targeted delivery of siRNAs by use of RGD-PEG-PCL has considerable potential for cancer treatment.

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