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RAFT Polymerization for the Synthesis of Tertiary Amine‐Based Diblock Copolymer Nucleic Acid Delivery Vehicles
Author(s) -
McClellan Annie K.,
Hao Taisen,
Brooks Tracy A.,
Smith Adam E.
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201700225
Subject(s) - copolymer , cationic polymerization , nucleic acid , tertiary amine , chemistry , ethylene glycol , polymerization , polymer chemistry , methacrylate , amine gas treating , gene delivery , combinatorial chemistry , organic chemistry , polymer , biochemistry , genetic enhancement , gene
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.