Efficient siRNA delivery using water soluble lipopolymer for anti-angiogenic gene therapy.
We examined the potential application of a non-viral gene carrier, water soluble lipopolymer (WSLP) for delivering siRNA targeting vascular endothelial growth factor (VEGF) in vitro and in vivo. WSLP was complexed with siRNA designed to inhibit human VEGF expression or scrambled siRNA as a control. WSLP readily formed nano-sized complexes ( approximately 100 nm) with siRNA and protected siRNAs from enzymatic degradation in serum conditioned media. WSLP/siRNA complexes were transfected in PC-3 cells derived from human prostate adenocarcinomas and, then the siRNA delivery efficiency of the complexes was evaluated by VEGF production inhibition assay. VEGF production was efficiently inhibited by the WSLP/siRNA complexes, while complexes of WSLP with scrambled siRNA did not show this inhibitory effect. WSLP/siRNA complexes reduced the VEGF production by 40% when compared to unmodified branched polyethylenimine (bPEI, MW=1800). Moreover, WSLP/siRNA complexes reduced tumor volume by 55% at 21 days, and by 65% at 28 days when compared to controls. These results indicate that WSLP has potential as a siRNA delivering agent and can be applied for anti-angiogenic tumor therapy.
Kim
Won Jong
WJ
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5820, USA.
Chang
Chien-Wen
CW
Lee
Minhyung
M
Kim
Sung Wan
SW
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011108:Polymers / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D014867:Water / Q000008:administration & dosage
D020533:Angiogenesis Inhibitors; D008055:Lipids; D011108:Polymers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D014867:Water