Nanoparticles targeted with NGR motif deliver c-myc siRNA and doxorubicin for anticancer therapy.
We have designed a PEGylated LPD (liposome-polycation-DNA) nanoparticle for systemic, specific, and efficient delivery of small interfering RNA (siRNA) into solid tumors in mice by modification with NGR (aspargine-glycine-arginine) peptide, targeting aminopeptidase N (CD13) expressed in the tumor cells or tumor vascular endothelium. LPD-PEG-NGR efficiently delivered siRNA to the cytoplasm and downregulated the target gene in the HT-1080 cells but not CD13(-) HT-29 cells, whereas nanoparticles containing a control peptide, LPD-PEG-ARA, showed only little siRNA uptake and gene silencing activity. LPD-PEG-NGR efficiently delivered siRNA into the cytoplasm of HT-1080 xenograft tumor 4 hours after intravenous injection. Three daily injections (1.2 mg/kg) of c-myc siRNA formulated in the LPD-PEG-NGR effectively suppressed c-myc expression and triggered cellular apoptosis in the tumor, resulting in a partial tumor growth inhibition. When doxorubicin (DOX) and siRNA were co-formulated in LPD-PEG-NGR, an enhanced therapeutic effect was observed.
Chen
Yunching
Y
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Wu
Jinzi J
JJ
Huang
Leaf
L
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D017209:Apoptosis; D018826:CD13 Antigens / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular; D016259:Genes, myc; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C526428:NGR peptide; D009842:Oligopeptides; D034741:RNA, Small Interfering; D004317:Doxorubicin; D018826:CD13 Antigens