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Updated: Sep 22, 2025
Gene-therapy Inspired Polycation Coating for Protection of DNA Origami Nanostructures
Published on: January 19, 2019
MAG versus PEG: Incorporating a Poly(MAG) Layer to Promote Colloidal Stability of Nucleic Acid/"Click Cluster"
Daniel J Buckwalter1, Antons Sizovs1, Nilesh P Ingle2
1Macromolecules and Interfaces Institute, Department of Chemistry, Virginia Polytechnic Institute, Blacksburg, Virginia 24061, United States.
Abstract:
Herein, we demonstrate the reversible addition-fragmentation chain transfer (RAFT) synthesis of an adamantane-conjugated glycopolymer, poly(2-methacrylamido-2-deoxy glucopyranose) (Ad-pMAG), as a hydrophilic coating to promote colloidal stability of click cluster-pDNA complexes in biological media. The Ad-pMAG is assembled via noncovalent interactions through inclusion complex formation between adamantane (Ad) and the β-cyclodextrin (βCD) core of the click cluster/pDNA and then further assembled with plasmid DNA to form polyplexes. Ad-pMAG incorporation was favorable over Ad-poly(ethylene glycol) (Ad-PEG) due to the enhanced colloidal stability of the click cluster/pDNA polyplex under physiological salt conditions at high N/P ratios. Interestingly, the uptake and reporter gene expression with polyplexes coated with the Ad-pMAG was much lower in HeLa cells than that observed with two glioma cell lines (U87 and U251 cells) in vitro, possibly indicating some delivery specificity.
