title: Receptor-mediated, tumor-targeted gene delivery using folate-terminated polyrotaxanes.
abstract: Safe and effective gene delivery is essential to the success of gene therapy. We synthesized and characterized a novel nonviral gene delivery system in which folate (FA) molecules were functioned as blockers on cationic polyrotaxanes (PR) composed of poly(ethylenimine) (PEI)(600)-grafted α-cyclodextrin rings linearized on polyethylene glycol to form FA-terminated PR-PEI(600) (FPP). The FA terminal caps of FPP target cell surfaces abundant in FA receptor (FR), a common feature of tumor cells. The structure of FPP was characterized by using (1)H nuclear magnetic resonance ((1)H NMR). The delivery particle was composed of chemically bonded PEG (4000), α-cyclodextrins (CD), and PEI (600 Da) at a molar ratio of 1:17:86.7, and the particle size and zeta potential of FPP/pDNA polyplexes were measured using dynamic light scattering. FPP/pDNA exhibited a lower cytotoxicity, strong specificity to FR, and high efficiency of delivering DNA to target cells in vitro and in vivo with the reporter genes. Furthermore, the FPP/DNA complex showed an enhanced antitumor effect in the nude mice compared with other delivery systems, such as PEI-25K. Together, these results suggest that FPP may be useful for gene therapy.
authors.affiliation: Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Chengxi
authors.initials: C
authors.lastname: Wang
authors.forename: Yueshan
authors.initials: Y
authors.lastname: Li
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Lu
authors.forename: Shuifang
authors.initials: S
authors.lastname: Chen
authors.forename: Jiandong
authors.initials: J
authors.lastname: Luo
authors.forename: Yongnan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jianhai
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D058973:Folate Receptors, GPI-Anchored / Q000235:genetics*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D043862:Rotaxanes / Q000737:chemistry*; D014162:Transfection / Q000379:methods; D023041:Xenograft Model Antitumor Assays; D047391:alpha-Cyclodextrins / Q000737:chemistry
chemical_list: D058973:Folate Receptors, GPI-Anchored; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; D011094:Polyethyleneimine; C032613:alpha-cyclodextrin