Multiscale simulation as a framework for the enhanced design of nanodiamond-polyethylenimine-based gene delivery

Hansung Kim, Han Bin Man, Biswajit Saha, Adrian M. Kopacz, One-Sun Lee, George C. Schatz, Dean Ho, Wing Kam Liu

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Nanodiamonds (NDs) are emerging carbon platforms with promise as gene/drug delivery vectors for cancer therapy. Specifically, NDs functionalized with the polymer polyethylenimine (PEI) can transfect small interfering RNAs (siRNA) in vitro with high efficiency and low cytotoxicity. Here we present a modeling framework to accurately guide the design of ND-PEI gene platforms and elucidate binding mechanisms between ND, PEI, and siRNA. This is among the first ND simulations to comprehensively account for ND size, charge distribution, surface functionalization, and graphitization. The simulation results are compared with our experimental results both for PEI loading onto NDs and for siRNA (c-Myc) loading onto ND-PEI for various mixing ratios. Remarkably, the model is able to predict loading trends and saturation limits for PEI and siRNA while confirming the essential role of ND surface functionalization in mediating ND-PEI interactions. These results demonstrate that this robust framework can be a powerful tool in ND platform development, with the capacity to realistically treat other nanoparticle systems.

Original languageEnglish
Pages (from-to)3791-3797
Number of pages7
JournalJournal of Physical Chemistry Letters
Volume3
Issue number24
DOIs
Publication statusPublished - 20 Dec 2012
Externally publishedYes

Fingerprint

Nanodiamonds
Polyethyleneimine
Genes
RNA
Small Interfering RNA
Graphitization
Charge distribution
Cytotoxicity
Drug delivery

Keywords

  • General Theory
  • Molecular Structure
  • Quantum Chemistry

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Multiscale simulation as a framework for the enhanced design of nanodiamond-polyethylenimine-based gene delivery. / Kim, Hansung; Man, Han Bin; Saha, Biswajit; Kopacz, Adrian M.; Lee, One-Sun; Schatz, George C.; Ho, Dean; Liu, Wing Kam.

In: Journal of Physical Chemistry Letters, Vol. 3, No. 24, 20.12.2012, p. 3791-3797.

Research output: Contribution to journalArticle

Kim, Hansung ; Man, Han Bin ; Saha, Biswajit ; Kopacz, Adrian M. ; Lee, One-Sun ; Schatz, George C. ; Ho, Dean ; Liu, Wing Kam. / Multiscale simulation as a framework for the enhanced design of nanodiamond-polyethylenimine-based gene delivery. In: Journal of Physical Chemistry Letters. 2012 ; Vol. 3, No. 24. pp. 3791-3797.
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