Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jul;14(7):908-22.
doi: 10.1002/mabi.201400061. Epub 2014 Mar 28.

Bioreducible polycations in nucleic acid delivery: past, present, and future trends

David Oupický  1 , Jing Li
Affiliations
Review

Bioreducible polycations in nucleic acid delivery: past, present, and future trends

David Oupický et al. Macromol Biosci. 2014 Jul.

Abstract

Polycations that are degradable by reduction of disulfide bonds are developed for applications in delivery of nucleic acids. This Feature Article surveys methods of synthesis of bioreducible polycations and discusses current understanding of the mechanism of action of bioreducible polyplexes. Emphasis is placed on the relationship between the biological redox environment and toxicity, trafficking, transfection activity, and in vivo behavior of bioreducible polycations and polyplexes.

Keywords: bioreducible; disulfides; gene delivery; polycations; polyplexes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Mechanism of thiol-disulfide exchange by oxidoreductases. Reproduced with permission.[39] Copyright 2002, Nature Publishing Group.
Figure 2
Figure 2
Synthetic approaches to bioreducible polycations.
Figure 3
Figure 3
Synthesis of bioreducible PAA by Michael polyaddition and examples of common amines used in the synthesis of linear and branched PAA.
Figure 4
Figure 4
Bioreducible crosslinkers used in the synthesis of bioreducible polycations.
Figure 5
Figure 5
Cationic peptides used in the synthesis of bioreducible polypeptides based on cysteine (left) and penicillamine with sterically hindered thiol (right).
Figure 6
Figure 6
Common thiolation methods of polyamines.
Figure 7
Figure 7
Structure of well-defined α,ω-bisthiol polycation based on N,N-dimethylaminoethyl methacrylate prepared by RAFT polymerization.[105]
Figure 8
Figure 8
Thiol-disulfide exchange polymerization of cationic lipoic acid derivative.[109]
Figure 9
Figure 9
Improved cytoplasmic release of DNA from polyplexes prepared with bioreducible PAA. Intracellular distribution of fluorescently labeled DNA delivered with PEI (A) or bioreducible PAA (B). (red dashed circles indicate cell nuclei) Reproduced with permission.[122] Copyright 2009, Elsevier Ltd.
Figure 10
Figure 10
Cytotoxicity of bioreducible polycations decreases with increasing disulfide content and cellular GSH levels. (Adapted from [151])
Scheme 1
Scheme 1
Principle of nucleic acid delivery by bioreducible polycations.
See this image and copyright information in PMC

References

    1. Bang EK, Lista M, Sforazzini G, Sakai N, Matile S. Chem. Sci. 2012;3:1752.
    1. Wu AM, Senter PD. Nat. Biotechnol. 2005;23:1137. - PubMed
    1. Corbett PT, Leclaire J, Vial L, West KR, Wietor J-L, Sanders JK, Otto S. Chem. Rev. 2006;106:3652. - PubMed
    1. Yoon JA, Kamada J, Koynov K, Mohin J, Nicolaÿ R, Zhang Y, Balazs AC, Kowalewski T, Matyjaszewski K. Macromolecules. 2011;45:142.
    1. Otto S, Furlan RL, Sanders JK. Science. 2002;297:590. - PubMed

Publication types