Phenylboronic acid-functionalized polymeric micelles with a HepG2 cell targetability

Biomaterials. 2013 Dec;34(38):10296-304. doi: 10.1016/j.biomaterials.2013.09.042. Epub 2013 Sep 24.

Abstract

Phenylboronic acid-functionalized amphiphilic block copolymer Pluronic-PMCC-BA was synthesized via ring-opening polymerization of 5-methyl-5-benzyloxycarbonyl-1,3-dioxan-2-one (MBC) with fumaric acid as a catalyst followed by the deprotection of carboxyl groups by catalyzed hydrogenation and the condensation of 3-aminophenylboronic acid with the copolymer side groups. Pluronic-PMCC-BA can form stable micelle solution by self-assembly in water. The phenylboronic acid groups are located at the shell of micelle as proved by (1)H NMR. The diameter of drug-free micelles is approximate 60 nm. Nano-spheres with narrow size distribution could be observed in the TEM image. MTT assay results show that Pluronic-PMCC-BA exhibits slight cytotoxicity when the polymer concentration is higher than 25 μg mL(-1). The toxicities of DOX@Pluronic-PMCC and DOX@Pluronic-PMCC-BA to COS7, HeLa, and HepG2 cell lines are similar with those of free DOX. Interestingly, phenylboronic acid groups located at the surface of Pluronic-PMCC-BA micelles can recognize HepG2 cells and promote the drug uptake of the cells, which are observed by confocal laser scanning microscopy (CLSM). The results imply that Pluronic-PMCC-BA would be a promising material for targeted drug delivery to the cancer cells.

Keywords: Controlled drug release; Copolymer; Pluronics; Polycarbonate; Polymeric micelle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boronic Acids / chemistry*
  • Drug Delivery Systems
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Micelles*
  • Polymers / adverse effects
  • Polymers / chemistry*

Substances

  • Boronic Acids
  • Micelles
  • Polymers
  • benzeneboronic acid