title: Self-aggregated pegylated poly (trimethylene carbonate) nanoparticles decorated with c(RGDyK) peptide for targeted paclitaxel delivery to integrin-rich tumors.
abstract: Cyclic RGD peptide-decorated polymeric micellar-like nanoparticles (MNP) based on PEGylated poly (trimethylene carbonate) (PEG-PTMC) were prepared for active targeting to integrin-rich cancer cells. An amphiphilic diblock copolymer, α-carboxyl poly (ethylene glycol)-poly (trimethylene carbonate) (HOOC-PEG-PTMC), was synthesized by ring-opening polymerization. The c(RGDyK) ligand, a cyclic RGD peptide that can bind to the integrin proteins predominantly expressed on the surface of tumor cells with high affinity and specificity, was conjugated to the NHS-Activated PEG terminus of the copolymer. The c(RGDyK)-functionalized PEG-PTMC micellar nanoparticles encapsulating PTX (c(RGDyK)-MNP/PTX) was fabricated by the emulsion/solvent evaporation technique and characterized in terms of morphology, size and zeta potential. Cellular uptake of c(RGDyK)-MNP/PTX was found to be higher than that of MNP/PTX due to the integrin protein-mediated endocytosis effect. In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that c(RGDyK)-MNP/PTX was more potent than those of MNP/PTX and Taxol. Pharmacokinetic study in rats demonstrated that the polymeric micellar nanoparticles significantly enhanced the bioavailability of PTX than Taxol. In vivo multispectral fluorescent imaging indicated that c(RGDyK)-MNP/PTX had high specificity and efficiency in tumor active targeting. Therefore, the results demonstrated that c(RGDyK)-decorated PEG-PTMC MNP developed in this study could be a potential vehicle for delivering hydrophobic chemotherapeutic agents to integrin-rich tumors.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Jiang
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.forename: Liangcen
authors.initials: L
authors.lastname: Chen
authors.forename: Xihui
authors.initials: X
authors.lastname: Gao
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Kitki
authors.initials: K
authors.lastname: Law
authors.forename: Jijin
authors.initials: J
authors.lastname: Gu
authors.forename: Yanzuo
authors.initials: Y
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Ren
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Ren
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000378:metabolism; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D003374:Coumarins; D004146:Dioxanes; D016023:Integrins; D010455:Peptides; D011108:Polymers; D013844:Thiazoles; C517282:coumarin 6; C059299:polytrimethylene carbonate; D011092:Polyethylene Glycols; D017239:Paclitaxel