Simulation and Experimental Assembly of DNA-Graft Copolymer Micelles with Controlled Morphology

Zonghui Wei, Yong Ren, John Michael Williford, Wei Qu, Kevin Huang, Shirley Ng, Hai Quan Mao*, Erik Luijten

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Nanoparticles formed through complexation of plasmid DNA and copolymers are promising gene-delivery vectors, offering a wide range of advantages over alternative delivery strategies. Notably, recent research has shown that the shape of these particles can be tuned, which makes it possible to gain understanding of their shape-dependent transfection properties. Whereas earlier methods achieved shape tuning through the use of block copolymers and variation of solvent polarity, here we demonstrate through a combined experimental and computational approach that the same degree of shape control can be achieved through the use of graft copolymers that are easier to synthesize and provide a wider range of parameters for shape control. Moreover, the approach presented here does not require the use of organic solvents. The simulation work provides insight into the mechanism governing the shape variation as well as an effective model to guide further design of nonviral gene-delivery vectors. Our experimental findings offer important opportunities for the facile and large-scale synthesis of biocompatible gene-delivery vectors with well-controlled shape and tunable transfection properties. The in vitro study shows that both micelle shape and transfection efficiency are strongly correlated with the key structural parameters of the graft copolymer carriers.

Original languageEnglish (US)
Pages (from-to)448-455
Number of pages8
JournalACS Biomaterials Science and Engineering
Volume1
Issue number6
DOIs
StatePublished - Dec 14 2015

Keywords

  • DNA packaging
  • micelles
  • self-assembly
  • shape control
  • transfection

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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