Issue 15, 2019

Structure-pDNA complexation and structure–cytotoxicity relationships of PEGylated, cationic aminoethyl-based polyacrylates with tunable topologies

Abstract

Well-defined, PEGylated aminoethyl-based polyacrylates bearing primary and tertiary ammonium moieties with linear and brush-like PEG topologies were successfully synthesized by successive RAFT copolymerization and amine deprotection. The resulting cationic polymers spontaneously associate with plasmid DNA (pDNA) via efficient condensation to form cationic polymer/pDNA bioconjugates. Effects of polymer structure on the pDNA complexation and on cell viability were assessed by gel retardation assays and MTT assays, respectively. Results demonstrated that bioconjugates with complete pDNA complexation were targeted using equal molar contents of primary and tertiary ammonium entities at low N/P ratios (1, 3 and 6) for cationic polymers without PEG, with linear PEG and with brush-like PEG, respectively. Moreover, when the primary and tertiary ammonium molar compositions were kept constant, linear and brush-like PEGylated aminoethyl-based polyacrylates were less toxic to the NIH/3T3 cell line compared to non-PEGylated counterparts. Also, brush-like PEGylated aminoethyl-based polyacrylates did not induce cytotoxicity even after incubation at high concentration (2 mg mL−1) and might therefore be envisioned as efficient pDNA vectors for gene therapy applications.

Graphical abstract: Structure-pDNA complexation and structure–cytotoxicity relationships of PEGylated, cationic aminoethyl-based polyacrylates with tunable topologies

Supplementary files

Article information

Article type
Paper
Submitted
14 Dec 2018
Accepted
07 Mar 2019
First published
12 Mar 2019

Polym. Chem., 2019,10, 1968-1977

Structure-pDNA complexation and structure–cytotoxicity relationships of PEGylated, cationic aminoethyl-based polyacrylates with tunable topologies

M. Le Bohec, K. Bonchouo Kenzo, S. Piogé, S. Mura, J. Nicolas, N. Casse, G. Forcher, L. Fontaine and S. Pascual, Polym. Chem., 2019, 10, 1968 DOI: 10.1039/C8PY01776J

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