Tunable nonenzymatic degradability of N -substituted polyaspartamide main chain by amine protonation and alkyl spacer length in side chains for enhanced messenger RNA transfection efficiency

Science and Technology of Advanced Materials
Mitsuru NaitoKanjiro Miyata

Abstract

Degradability of polycations under physiological conditions is an attractive feature for their use in biomedical applications, such as the delivery of nucleic acids. This study aims to design polycations with tunable nonenzymatic degradability. A series of cationic N-substituted polyaspartamides were prepared to possess primary amine via various lengths of alkyl spacers in side chains. The degradation rate of each polyaspartamide derivative was determined by size exclusion chromatography under different pH conditions. The N-substituted polyaspartamide containing a 2-aminoethyl moiety in the side chain (PAsp(AE)) showed considerable degradability under physiological conditions (pH 7.4, 37 °C). In contrast, the N-substituted polyaspartamides bearing a longer alkyl spacer in the side chain, i.e. the 3-aminopropyl (PAsp(AP)) and 4-aminobutyl moieties (PAsp(AB)), more strongly suppressed degradation. Further, a positive correlation was observed between the degradation rate of N-substituted polyaspartamides and a deprotonation degree of primary amines in their side chains. Therefore, we conclude that the deprotonated primary amine in the side chain of N-substituted polyaspartamides can induce the degradation of the main chain through...Continue Reading

References

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Citations

Sep 18, 2020·Science and Technology of Advanced Materials·Takanori AkagiPeng Mi
May 7, 2021·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kanjiro Miyata
Aug 28, 2021·International Journal of Molecular Sciences·Guangyan ZhangChenhui Bao

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Methods Mentioned

BETA
transfection
size exclusion chromatography
nuclear magnetic resonance
flow
Flow cytometry

Software Mentioned

Excel
ChromNAV

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