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Incorporation of Indole Significantly Improves the Transfection Efficiency of Guanidinium-Containing Poly(methacrylamide)s

preprint
submitted on 17.01.2020 and posted on 20.01.2020 by Ceren Cokca, Leon Zartner, Ilja tabujew, Dagmar Fischer, Kalina Peneva

In this study, we report a highly efficient transfection agent based on terpolymer consisting of N-(2-hydroxypropyl)methacrylamide (HPMA), N-(3-guanidinopropyl) methacrylamide (GPMA), and N-(2-indolethyl)methacrylamide (IEMA) monomers by analogy to the amphipathic cell penetrating peptides containing tryptophan and arginine residues. The incorporation of the indole bearing monomer led to successful plasmid DNA condensation even at nitrogen to phosphate (N/P) ratio 1. The hydrodynamic diameter of polyplexes was determined to be below 200 nm for all N/P ratios. The transfection studies demonstrated 200- fold increase of the transgene expression in comparison to P(HPMA-co-GPMA) with the same guanidinium content. This study reveals the strong potential of the indole group as side chain pending group that can increase the cellular uptake of polymers and the transfection efficiency of the respective polyplexes.

Funding

Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – project number 316213987 – SFB 1278, Project B03

History

Email Address of Submitting Author

kalina.peneva@uni-jena.de

Institution

Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena

Country

Germany

ORCID For Submitting Author

0000-0001-5578-3266

Declaration of Conflict of Interest

The authors declare no conflict of interest.

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