Synthesis of novel folic acid-functionalized biocompatible block copolymers by atom transfer radical polymerization for gene delivery and encapsulation of hydrophobic drugs

Biomacromolecules. 2005 Mar-Apr;6(2):1085-96. doi: 10.1021/bm049271i.

Abstract

Two synthetic routes to folic acid (FA)-functionalized diblock copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and either 2-(dimethylamino)ethyl methacrylate [DMA] or 2-(diisopropylamino)ethyl methacrylate [DPA] were explored. The most successful route involved atom transfer radical polymerization (ATRP) of MPC followed by the tertiary amine methacrylate using a 9-fluorenylmethyl chloroformate (Fmoc)-protected ATRP initiator. Deprotection of the Fmoc groups produced terminal primary amine groups, which were conjugated with FA to produce two series of novel FA-functionalized biocompatible block copolymers. Nonfunctionalized MPC-DMA diblock copolymers have been previously shown to be effective synthetic vectors for DNA condensation; thus, these FA-functionalized MPC-DMA diblock copolymers appear to be well suited to gene therapy applications based on cell targeting strategies. In contrast, the FA-MPC-DPA copolymers are currently being evaluated as pH-responsive micellar vehicles for the delivery of highly hydrophobic anticancer drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemical synthesis*
  • Drug Carriers / chemical synthesis*
  • Drug Compounding
  • Folic Acid*
  • Genetic Therapy
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Structure
  • Polymers / chemical synthesis*
  • Polymers / therapeutic use

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Polymers
  • Folic Acid