Folate-functionalized polymeric micelles for tumor targeted delivery of a potent multidrug-resistance modulator FG020326

Xiaoqiang Yang, Wenjing Deng, Liwu Fu, Elvin Blanco, Jinming Gao, Daping Quan, Xintao Shuai

Research output: Contribution to journalArticle

78 Citations (Scopus)

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(ε-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 ε-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°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 KBv200 cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KBv200 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.

Original languageEnglish (US)
Pages (from-to)48-60
Number of pages13
JournalJournal of Biomedical Materials Research - Part A
Volume86
Issue number1
DOIs
StatePublished - Jul 2008

Fingerprint

Micelles
Folic Acid
Modulators
Polyethylene glycols
Tumors
Copolymers
Rhodamine 123
Addition reactions
Chemotherapy
Ring opening polymerization
P-Glycoprotein
Glycoproteins
Vincristine
Cytotoxicity
Acids
methyl 3-(4-(4,5-bis(4-(isopropyl(methyl)amino)phenyl)-1H-imidazol-2-yl)phenyl)acrylate
Encapsulation
Block copolymers
Chemical reactions
Assays

Keywords

  • Folate functionalization
  • Multidrug resistance
  • Poly (ethylene glycol)-poly(ε- caprolactone)
  • Polymeric micelles
  • Tumor targeting

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

Folate-functionalized polymeric micelles for tumor targeted delivery of a potent multidrug-resistance modulator FG020326. / Yang, Xiaoqiang; Deng, Wenjing; Fu, Liwu; Blanco, Elvin; Gao, Jinming; Quan, Daping; Shuai, Xintao.

In: Journal of Biomedical Materials Research - Part A, Vol. 86, No. 1, 07.2008, p. 48-60.

Research output: Contribution to journalArticle

Yang, Xiaoqiang ; Deng, Wenjing ; Fu, Liwu ; Blanco, Elvin ; Gao, Jinming ; Quan, Daping ; Shuai, Xintao. / Folate-functionalized polymeric micelles for tumor targeted delivery of a potent multidrug-resistance modulator FG020326. In: Journal of Biomedical Materials Research - Part A. 2008 ; Vol. 86, No. 1. pp. 48-60.
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AB - 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(ε-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 ε-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°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 KBv200 cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KBv200 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.

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