Cationic Galactose-Conjugated Copolymers for Epidermal Growth Factor (EGFR) Knockdown in Cervical Adenocarcinoma
Stephen Quan1, Piyush Kumar2, Ravin Narain2
1Donadeo Innovation Centre for Engineering, Department of Chemical and Materials Engineering, and ‡Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Abstract:
Glycopolymers of statistical and block configurations were synthesized from 2-lactobionamidoethyl methacrylamide (LAEMA) and 2-aminoethyl methacrylamide hydrochloride (AEMA) by the reversible addition-fragmentation chain transfer (RAFT) polymerization. These cationic glycopolymers were found to form very stable polyplexes with EGFR siRNA as determined by dynamic light scattering and agarose gel electrophoresis. The polyplexes revealed to be very stable even in the presence of serum proteins. Transfection studies of the glycopolymer-EGFR siRNA polyplexes were achieved in HeLa cells to determine the EGFR knockdown efficiency, cellular uptake and cytotoxicity. In this study, the block copolymer with the shortest AEMA segment was the most effective in EGFR gene silencing, however this block copolymer revealed to be slightly more toxic as compared to the statistical copolymers studied at higher w/w ratios. In addition, gene silencing of up to 80-85% was achieved with this low-molecular-weight block copolymer.
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