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Visualization of Surface-tethered Large DNA Molecules with a Fluorescent Protein DNA Binding Peptide
Published on: June 23, 2016
Subtle changes in surface-tethered groups on PEGylated DNA nanoparticles significantly influence gene transfection
Xiyu Ke1, Zonghui Wei2, Ying Wang1
1Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, United States; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, United States.
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.
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