title: Tumor specific delivery and therapy by double-targeted nanostructured lipid carriers with anti-VEGFR-2 antibody.
abstract: Vascular endothelial growth factor receptors (VEGFRs) are overexpressed on the surface of a variety of tumor cells and on tumor neovasculature in situ, which are potential targets for "double targeting" (tumor- and vascular-targeting) tumor therapy. This study aimed to develop a VEGFR-mediated drug delivery system to target chemotherapeutic agents to VEGFR-overexpressed tumor cells and tumor neovasculature endothelial cells in vitro and in vivo. An antibody modified docetaxel (DTX)-loaded targeted nanostructured lipid carrier (tNLC) was designed and prepared with DSPE-PEG-NH(2) as linker. The cellular cytotoxicity, cellular uptake, in vivo therapeutic effect and biodistribution of tNLC were investigated. The tNLC showed a particle size about 168 nm with encapsulation efficiency >95%, drug loading 5.55 ± 0.06% (w/w) and an average ligand coupling efficiency of 3.34 ± 2.63%. Cytotoxicity of tNLC against three human cell lines and one murine malignant melanoma was superior to that of Duopafei and nontargeted NLC (nNLC). The tNLC also showed better tolerance and antitumor efficacy in a murine model bearing B16 compared with Duopafei or nNLC. The studies on cellular uptake and biodistribution indicated that the better antitumor efficacy of tNLC was attributed to the increased accumulation of drug in both tumor and tumor vasculature. These findings suggested that tNLC designed to bind specifically to VEGFR-2 can be used to deliver DTX to the tumor vasculature and tumor and may inhibit tumor growth.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Ji'nan 250012, China.
authors.forename: Donghua
authors.initials: D
authors.lastname: Liu
authors.forename: Fengxi
authors.initials: F
authors.lastname: Liu
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007260:Infusion Pumps; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry; D043823:Taxoids / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D040301:Vascular Endothelial Growth Factor Receptor-2