Macromolecular Bioscience
Macromolecular Bioscience
5 years ago

RAFT Polymerization for the Synthesis of Tertiary Amine-Based Diblock Copolymer Nucleic Acid Delivery Vehicles

RAFT Polymerization for the Synthesis of Tertiary Amine-Based Diblock Copolymer Nucleic Acid Delivery Vehicles
Adam E. Smith, Annie K. McClellan, Tracy A. Brooks, Taisen Hao
The synthesis and characterization of a family of nine pH-responsive, diblock copolymers designed to effectively deliver nucleic acids are 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 (DPs) 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 Michigan Cancer Foundation-7 (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. The development of pH-responsive block copolymer nucleic acid delivery vehicles is reported. Nine block copolymers with varying tertiary amine-containing cationic blocks are utilized to complex and deliver oligonucleotides in vitro. 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/mabi.201700225

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