MAG versus PEG: Incorporating a poly(MAG) layer to promote colloidal stability of nucleic acid/"click cluster" complexes

Daniel J. Buckwalter; Antons Sizovs; Nilesh P. Ingle; Theresa M. Reineke

doi:10.1021/mz300081d

MAG versus PEG: Incorporating a poly(MAG) layer to promote colloidal stability of nucleic acid/"click cluster" complexes

Daniel J. Buckwalter, Antons Sizovs, Nilesh P. Ingle, Theresa M. Reineke

Chemistry (Twin Cities)

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Herein, we demonstrate the reversible addition-fragmentation chain transfer (RAFT) synthesis of an adamantane-conjugated glycopolymer, poly(2- methacrylamido-2-deoxy glucopyr-anose) (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. (Figure presented)

Original language	English (US)
Pages (from-to)	609-613
Number of pages	5
Journal	ACS Macro Letters
Volume	1
Issue number	5
DOIs	https://doi.org/10.1021/mz300081d
State	Published - May 15 2012

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title = "MAG versus PEG: Incorporating a poly(MAG) layer to promote colloidal stability of nucleic acid/{"}click cluster{"} complexes",

abstract = "Herein, we demonstrate the reversible addition-fragmentation chain transfer (RAFT) synthesis of an adamantane-conjugated glycopolymer, poly(2- methacrylamido-2-deoxy glucopyr-anose) (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. (Figure presented)",

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AU - Sizovs, Antons

AU - Ingle, Nilesh P.

AU - Reineke, Theresa M.

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N2 - Herein, we demonstrate the reversible addition-fragmentation chain transfer (RAFT) synthesis of an adamantane-conjugated glycopolymer, poly(2- methacrylamido-2-deoxy glucopyr-anose) (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. (Figure presented)

AB - Herein, we demonstrate the reversible addition-fragmentation chain transfer (RAFT) synthesis of an adamantane-conjugated glycopolymer, poly(2- methacrylamido-2-deoxy glucopyr-anose) (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. (Figure presented)

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MAG versus PEG: Incorporating a poly(MAG) layer to promote colloidal stability of nucleic acid/"click cluster" complexes

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