Cationic star copolymers obtained by the arm first approach for gene transfection

Abstract

Cationic polymers can be used as vectors to transport and efficiently protect nucleic acids. In this work we describe the synthesis of dense star-like polymers of 2-dimethylaminoethyl acrylate (DMAEA) and 2-dimethylaminoethyl methacrylate (DMAEMA) and the hydrolysis of the DMAEA units side chains for the complexation and release of nucleic acids. The successful chain extension of p(DMAEA₈₀-stat-DMAEMA₂₀) with acrylamide monomers allowed the preparation of stars by the arm-first approach. Soluble stars with a high number of well-defined arms (N_arm ∼55–100) were obtained with the introduction of non-cationic N-acrylmorpholine (NAM) prior to the crosslinking step. The influence of the architecture on the hydrolysis of the DMAEA units side chains was studied, with only small differences observed compared to the corresponding arm. All stars were able to complex a large (10 000 basepairs) plasmid DNA encoding for green fluorescent protein (GFP), and transfect HEK293T cells, with the larger, more charged star structure leading to higher transfection efficiency. Although the transfection efficiency is lower than that of the gold standard polyethylenimine (PEI), the stars much lower toxicity, at concentrations as high as 1 mg mL⁻¹, make them viable transfection agents.