title: Folate-functionalized polymeric micelles for tumor targeted delivery of a potent multidrug-resistance modulator FG020326.
abstract: To overcome multidrug resistance (MDR) existing in tumor chemotherapy, polymeric micelles encoded with folic acid on the micelle surface were prepared with the encapsulation of a potent MDR modulator, FG020326. The micelles were fabricated from diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable poly(epsilon-caprolactone) (PCL) with folate attached to the distal ends of PEG chains. The folate-conjugated copolymers, folate-PEG-PCL, were synthesized by multistep chemical reactions. First, allyl-terminated copolymer (allyl-PEG-PCL) was synthesized through a ring-opening polymerization of epsilon-caprolactone in bulk employing monoallyl-PEG as a macroinitiator. Second, the allyl terminal groups of copolymers were converted into primary amino groups by a radical addition reaction, followed by conjugation of the carboxylic group of folic acid. In vitro studies at 37 degrees C demonstrated that FG020326 release from micelles at pH 5.0 was faster than that at pH 7.4. Cytotoxicity studies with MTT assays indicated that folate-functionalized and FG020326-loaded micelles resensitized the cells approximately five times more than their folate-free counterparts (p < 0.01) in human KB(v200) cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KB(v200) cells revealed that when cells were pretreated with folate-attached and FG020326-loaded micelles, the P-glycoprotein (P-gp) drug efflux function was significantly inhibited.
authors.affiliation: BME Center, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Deng
authors.forename: Liwu
authors.initials: L
authors.lastname: Fu
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
authors.forename: Daping
authors.initials: D
authors.lastname: Quan
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
mesh_terms: D000179:Acrylates / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D004337:Drug Carriers; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D005026:Ethylene Glycols / Q000737:chemistry*; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000008:administration & dosage*; D020128:Inhibitory Concentration 50; D008422:Materials Testing; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D020112:Rhodamine 123 / Q000494:pharmacology
chemical_list: D000179:Acrylates; D001672:Biocompatible Materials; D002264:Carboxylic Acids; D004337:Drug Carriers; D005026:Ethylene Glycols; D007093:Imidazoles; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C531580:methyl 3-(4-(4,5-bis(4-(isopropyl(methyl)amino)phenyl)-1H-imidazol-2-yl)phenyl)acrylate; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D020112:Rhodamine 123; D011092:Polyethylene Glycols; D005492:Folic Acid