The synthesis and characterization of a family of pH-responsive, diblock copolymers designed to effectively deliver nucleic acids is reported. The stabilizing A block is comprised of an oligo(ethylene glycol) methyl ether methacrylate to impart water solubility. The cationic blocks of varying degrees of polymerization are derived from three pH-responsive, tertiary amine-containing methacrylates capable of complexing negatively charged nucleic acids. The cytotoxicity studies utilizing human embryonic kidney cells (HEK-293) and MCF-7 breast cancer cells indicate no decrease of cell viability with the diblock copolymers, with the exception of the two highest DPs of the cationic blocks with ethyl-substitutes tertiary amine. Gene knockdown experiments indicate high siRNA delivery and MYC gene knockdown in MCF-7 breast cancer cells for eight of the nine studied block copolymers. The results of the current study enable further development of the pH-responsive copolymer family for promising nucleic acid delivery vehicles applicable for clinical use.

RAFT polymerization for the synthesis of tertiary amine-based diblock copolymer nucleic acid delivery vehicles

2019 Spring National Meeting

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