RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment

• Published in: Journal of controlled release Vol. 160; no. 2; pp. 177 - 181
• Main Authors: Yonenaga, Norihito, Kenjo, Eriya, Asai, Tomohiro, Tsuruta, Atsushi, Shimizu, Kosuke, Dewa, Takehisa, Nango, Mamoru, Oku, Naoto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-06-2012
• Subjects: Active targeting; Animals; Cancer therapy; Cations; Cell Line, Tumor; cholesterol; Drug Carriers - chemistry; Ethylenediamines - chemistry; genes; Genetic Therapy - methods; image analysis; intravenous injection; Liposome; Liposomes; luciferase; lungs; Male; melanoma; Melanoma, Experimental - genetics; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; metastasis; Mice; Mice, Inbred C57BL; neoplasm cells; Oligopeptides - chemistry; Organophosphates - chemistry; Polycation; Polyethylene Glycols - chemistry; RNA Interference; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - genetics; RNA, Small Interfering - therapeutic use; siRNA; small interfering RNA; therapeutics; Xenograft Model Antitumor Assays; Liposome; Active targeting; siRNA; Polycation; Cancer therapy
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.10.004

For the purpose of systemic delivery of siRNA, we previously developed polycation liposomes (PCLs) containing dicetylphosphate-tetraethylenepentamine (DCP-TEPA) as an effective siRNA carrier. In the present study, to endow these PCLs (TEPA-PCL) actively target cancer cells and angiogenic vessels, we decorated the PCLs with cyclic RGD, by using cyclic RGD-grafted distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG), and investigated the usefulness of this type of carrier (RGD-PEG-PCL) for active targeting. Firstly, the gene-silencing efficacy of siRNA for luciferase (siLuc2) formulated in RGD-PEG-PCL (RGD-PEG-PCL/siLuc2) was examined in vitro by using B16F10-luc2 murine melanoma cells stably expressing the luciferase 2 gene, where the siRNA was grafted with cholesterol at the 3′-end of the sense strand (siRNA-C) for the stable association of the siRNA with the PCL. RGD-PEG-PCL/siLuc2 showed high knockdown efficiency compared with siLuc2 formulated in PEGylated TEPA-PCL without cyclic RGD (PEG-PCL). Next, the gene-silencing efficacy of RGD-PEG-PCL/siLuc2 was examined in vivo by use of B16F10-luc2 lung metastatic model mice. The intravenous injection of RGD-PEG-PCL/siLuc2 showed high knockdown efficiency against metastatic B16F10-luc2 tumors in the lungs of the mice, as assessed with an in vivo imaging system. These data strongly suggest that systemic and active targeting siRNA delivery using RGD-PEG-PCL is useful for cancer RNAi therapy.
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