Surface-modified LPD nanoparticles for tumor targeting.
We have developed a tumor-targeted LPD formulation (liposome-polycation-DNA complex) for siRNA. With surface modification, the targeted, PEGylated LPD increased the delivery efficiency by four-fold and the gene-silencing effect by two- to three-fold. Downregulation of survivin in human lung cancer cells by targeted LPD induced 90% of apoptosis and sensitized the cells to cisplatin by four-fold. PEGylated LPD formulation also significantly improved the tumor localization of siRNA in the NCI-H460 human lung cancer xenograft model. The tumor appeared to be the major uptake organ for siRNA formulated in surface-modified LPD. Our encouraging results indicate that surface-modified LPD may be a potent carrier for RNAi-based tumor therapy.
Li
Shyh-Dar
SD
Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Huang
Leaf
L
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D004357:Drug Synergism; D020868:Gene Silencing / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins; D053758:Nanoparticles; D009363:Neoplasm Proteins; D011092:Polyethylene Glycols; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077022:Survivin; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
C107489:BIRC5 protein, human; D015415:Biomarkers; D004337:Drug Carriers; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D011092:Polyethylene Glycols; D002945:Cisplatin