Thiourea-functional bioreducible poly(amido amine)s in gene delivery

M. Rachèl Elzes, Guoying Si, Johan F.J. Engbersen, Jos M.J. Paulusse

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

1 Citation (Scopus)

Abstract

Successful gene therapy relies on gene delivery vectors with high transfection efficiency and minimal toxicity. Bioreducible cationic polymers were developed as nonviral gene delivery vectors due to their large capacity to carry genes and highly modular synthesis. Poly(amido amine)s (PAAs) with disulfide linkages along the backbone and varying amounts of thiourea moieties in the side-chains were prepared via Michael-type polyaddition of 1-(4-aminobutyl)-3-(pyridin-3-yl)thiourea to N,N'-cystamine bisacrylamide (CBA). The thiourea-containing PAAs are able to condensate plasmid DNA into nanosized polyplexes with positive surface charge as determined by dynamic light scattering and zeta-potential measurements. The plasmid DNA is readily liberated from the polyplexes upon exposure to reducing environment, as confirmed by gel electrophoresis after treatment with the reducing agent dithiothreitol. Polyplexes of thiourea-functionalized PAAs show no discernible toxicity and markedly higher transfection efficiencies on COS-7 cells as compared to polyplexes of the frequently applied branched polyethylenimine (PEI, 25 kDa), as well as the PAA analogue obtained via polyaddition of 1-amino-4-butanol (ABOL) to CBA (pABOL), at their optimal transfection conditions. The high transfection capacity of the thiourea-functionalized PAAs remains largely unaffected in the presence of 10% serum, while the transfection efficiencies of PEI and pABOL are considerably reduced under these conditions. The results demonstrate the potential of thiourea functionalization of PAAs in enhancing their transfection efficiencies while maintaining minimal toxicities.

Original languageEnglish
Title of host publicationTargeted Nanosystems for Therapeutic Applications
Subtitle of host publicationNew Concepts, Dynamic Properties, Efficiency, and Toxicity
EditorsMarc A. Ilies, Kazuo Sakurai
PublisherAmerican Chemical Society
Chapter5
Pages93-117
Number of pages25
Volume1309
ISBN (Electronic)9780841233836
DOIs
Publication statusPublished - 1 Jan 2019

Publication series

NameACS Symposium Series
Volume1309
ISSN (Print)0097-6156
ISSN (Electronic)1947-5918

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