Systemic delivery of small interfering RNA by use of targeted polycation liposomes for cancer therapy.
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.
Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52–1 Yada, Suruga-ku, Shizuoka 422–8526, Japan.
Eriya
E
Kenjo
Tomohiro
T
Asai
Norihito
N
Yonenaga
Hidenori
H
Ando
Takayuki
T
Ishii
Kentaro
K
Hatanaka
Kosuke
K
Shimizu
Yugo
Y
Urita
Takehisa
T
Dewa
Mamoru
M
Nango
Hideo
H
Tsukada
Naoto
N
Oku
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005029:Ethylenediamines / Q000737:chemistry; D008081:Liposomes; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010755:Organophosphates / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D055291:Salivary alpha-Amylases / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D005029:Ethylenediamines; D008081:Liposomes; D010755:Organophosphates; D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C507169:cyclic arginine-glycine-aspartic acid peptide; C467480:vascular endothelial growth factor A, mouse; C002290:dicetylphosphate; D011092:Polyethylene Glycols; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; C524799:Amy1 protein, mouse; D055291:Salivary alpha-Amylases; C034269:tetraethylenepentamine