MAG versus PEG: Incorporating
a Poly(MAG) Layer to
Promote Colloidal Stability of Nucleic Acid/“Click Cluster”
Complexes
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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