Parallel Synthesis and Screening of Polymers for Nonviral Gene Delivery


We describe the parallel synthesis and in vitro evaluation of a cationic polymer library for the discovery of nonviral gene delivery vectors. The library was synthesized based on the ring-opening polymerization reaction between epoxide groups of diglycidyl ethers and the amines of (poly)amines. Parallel screening of soluble library constituents led to the identification of lead polymers with high DNA-binding efficacies. Transfection efficacies of lead polymers were evaluated using PC3-PSMA human prostate cancer cells and murine osteoblasts in the absence and presence of serum. In vitro experiments resulted in the identification of a candidate polymer that demonstrated significantly higher transfection efficacies and lower cytotoxicities than poly(ethyleneimine) (pEI), the current standard for polymeric transfection agents. In addition, polymers that demonstrated moderately higher and comparable transfection efficacies with respect to pEI were also identified. Our results demonstrate that high-throughput synthesis and screening of polymers is a powerful approach for the identification of novel nonviral gene delivery agents.


Chemical and Biochemical Engineering

Keywords and Phrases

1 (2 aminoethyl)piperidine; 1,4 bis(3 aminpropyl)piperazine; 1,4 butanediol diglycidyl ether; 1,4 cyclohexanedimethanol diglycidyl ether; 3,3' diamino n methyl dipropylamine; 4 vinylcyclohexene diepoxide; 4,7,10 trioxa 1,13 tridecanediamine; amine; aniline; butylamine; diethylenetriamine; epoxide; ether derivative; ethylenediamine; ethyleneglycol diglycidyl ether; glycerol diglycidyl ether; n (2 aminoethyl) 1,3 propanediamine; neopentylglycol diglycidyl ether; pentaethylenehexamine; poly(propyleneglycol)diglycidyl ether; polyethyleneglycol diglycidyl ether; polyethyleneimine; polymer; unclassified drug; cation; DNA; polymer, animal cell; article; controlled study; cytotoxicity; DNA binding; drug screening; drug synthesis; human; human cell; in vitro study; nonhuman; nonviral gene delivery system; priority journal; ring opening metathesis polymerization; cell survival; chemical structure; chemistry; combinatorial chemistry; drug effect; genetics; synthesis; transgene; tumor cell line, Cations; Cell Line, Tumor; Cell Survival; Combinatorial Chemistry Techniques; DNA; Humans; Molecular Structure; Polymers; Transgenes

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Document Type

Article - Journal

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© 2009 American Chemical Society (ACS), All rights reserved.

Publication Date

01 Feb 2009

PubMed ID