Subtle changes in surface-tethered groups on PEGylated DNA nanoparticles significantly influence gene transfection and cellular uptake

Xiyu Ke, Zonghui Wei, Ying Wang, Sabrina Shen, Yong Ren, John Michael Williford, Erik Luijten*, Hai Quan Mao

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

PEGylation strategy has been widely used to enhance colloidal stability of polycation/DNA nanoparticles (NPs)for gene delivery. To investigate the effect of polyethylene glycol (PEG)terminal groups on the transfection properties of these NPs, we synthesized DNA NPs using PEG-g-linear polyethyleneimine (lPEI)with PEG terminal groups containing alkyl chains of various lengths with or without a hydroxyl terminal group. For both alkyl- and hydroxyalkyl-decorated NPs with PEG grafting densities of 1.5, 3, or 5% on lPEI, the highest levels of transfection and uptake were consistently achieved at intermediate alkyl chain lengths of 3 to 6 carbons, where the transfection efficiency is significantly higher than that of nonfunctionalized lPEI/DNA NPs. Molecular dynamics simulations revealed that both alkyl- and hydroxyalkyl-decorated NPs with intermediate alkyl chain length exhibited more rapid engulfment than NPs with shorter or longer alkyl chains. This study identifies a new parameter for the engineering design of PEGylated DNA NPs.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume19
DOIs
StatePublished - Jul 2019

Keywords

  • Cellular uptake
  • Molecular dynamics simulation
  • PEG terminal group
  • PEGylated DNA nanoparticles
  • Transfection

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Subtle changes in surface-tethered groups on PEGylated DNA nanoparticles significantly influence gene transfection and cellular uptake'. Together they form a unique fingerprint.

  • Cite this