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

20 January 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

guanidinium
indole
gene delivery
methacrylamide

Supplementary materials

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Cocka et al SI
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