Synthesis and in vitro evaluation of novel star-shaped block copolymers (blocked star vectors) for efficient gene delivery

Bioconjug Chem. 2007 Nov-Dec;18(6):2037-44. doi: 10.1021/bc070045q. Epub 2007 Oct 9.

Abstract

Novel 4-branched diblock copolymers consisting of cationic chains as an inner domain and nonionic chains as an outer domain were prepared by iniferter-based living radial polymerization and evaluated as a polymeric transfectant. The cationic polymerization of 3-(N,N-dimethylamino)propyl acrylamide (DMAPAAm) using 1,2,4,5-tetrakis( N,N-diethyldithiocarbamylmethyl)benzene as a 4-functional iniferter followed by the nonionic block polymerization of N,N-dimethylacrylamide (DMAAm) afforded 4-branched diblock copolymers with controlled compositions. By changing the solution or irradiation conditions, 4-branched PDMAPAAms with molecular weights of 10,000, 20,000, and 50,000 were synthesized. In addition, by graft polymerization, PDMAPAAm-PDMAAm blocked copolymers with copolymer composition (unit ratio of DMAAm/DMAPAAm) ranging from 0.18 to 1.0 for each cationic polymer were synthesized. All polymers were shown to interact with and condense plasmid DNA to yield polymer/DNA complexes (polyplexes). A transfection study on COS-1 cells showed that the polyplexes from block copolymers with cationic chain length of approximately 50,000 and a nonionic chain length of 30,000, which were approximately 200 nm in diameter and very stable in aqueous media, had the most efficient luciferase activity with minimal cellular cytotoxicity under a charge ratio of 20 (vector/pDNA). The PDMAPAAm-PDMAAm-blocked, star-shaped polymers are an attractive novel class of nonviral gene delivery systems.

MeSH terms

  • Acrylamides / chemistry*
  • Animals
  • COS Cells
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Molecular Weight
  • Plasmids / genetics
  • Polymers / chemical synthesis*
  • Polymers / chemistry
  • Polymers / toxicity
  • Transfection / methods*

Substances

  • Acrylamides
  • N,N-dimethylaminopropylacrylamide
  • Polymers
  • N,N-dimethylacrylamide