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 journalArticlepeer-review

80 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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