Molecular Therapy · 2010 · 182 citations · 20 references
PharmacyOncologyPharmaceuticsDrug DeliveryNanoparticle Drug DeliveryTargeted Drug DeliveryCancer Drug DeliveryCancer NanomedicineLiposome-based DeliveryNanoparticle DesignNucleic Acid DeliverySmall Interfering Rna DeliveryGene Delivery To Cancer CellsMultiple Daily InjectionsNanoparticle Delivery VectorsNanoparticle-based ChemotherapyNanoparticlesTargeted Gene SilencingTumor-targeted Drug DeliveryTumor-targeting Peptides
A PEGylated liposome‑polycation‑DNA (LPD) nanoparticle was engineered with an NGR peptide to target CD13 on tumor cells and vasculature, enabling systemic, specific delivery of siRNA into solid tumors in mice. The LPD‑PEG‑NGR formulation efficiently delivered c‑myc siRNA to HT‑1080 cells and xenografts, downregulated c‑myc, induced apoptosis, partially inhibited tumor growth, and when co‑loaded with doxorubicin, produced an enhanced therapeutic effect.
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. 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.
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Anti-cancer activity of targeted pro-apoptotic peptides
H. Michael Ellerby, Wadih Arap, Lisa Ellerby et al. · Nature Medicine · 1999 · 930 citations
Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis.
Renata Pasqualini, Erkki Koivunen, Renate Kain et al. · PubMed · 2000 · 867 citations
Medicine, Oncology, Pharmacology +16