Issue 39, 2014

Co-caged gold nanoclusters and methyl motifs lead to detoxification of dendrimers and allow cytosolic access for siRNA transfection

Abstract

Nonviral vectors used in gene delivery, such as cationic polymers and dendrimers, exhibit problems of inherent toxicity and inefficient cytosolic access that must be overcome. In this work, a simple co-caging strategy focused on overcoming the two limitations of dendrimers for siRNA transfection is reported. By embedding gold nanoclusters within a dendrimer, the structure of the dendrimer becomes compact and allows an irreversible backfolding of exterior primary amines from the branch to the core, which dramatically eliminates dendrimer toxicity and enhances safety. Gold nanoclusters with strong emissions can confer a trackable function to dendrimers acting as a transfection vector (TV) for siRNA transfection. In order to maximize efficiency of complexing with siRNA, the TV further incorporated caged methyl motifs, transforming the partially tertiary amines into quaternary ammonium ions to form a methylated TV (MTV). The cellular responses to the MTV were similar to those of the TV, but the responses to the MTV can also enhance cytosolic access to better deliver siRNA for mRNA knockdown. This finding offers a novel perspective to facilitate the use of various cationic polymers for detoxification in biological applications through a co-caging strategy without further chemical modifications.

Graphical abstract: Co-caged gold nanoclusters and methyl motifs lead to detoxification of dendrimers and allow cytosolic access for siRNA transfection

Supplementary files

Article information

Article type
Paper
Submitted
14 Jul 2014
Accepted
31 Jul 2014
First published
05 Sep 2014

J. Mater. Chem. B, 2014,2, 6730-6737

Author version available

Co-caged gold nanoclusters and methyl motifs lead to detoxification of dendrimers and allow cytosolic access for siRNA transfection

C. Chien, C. Liu, Z. Wu, P. Chen, C. Chu and S. Lin, J. Mater. Chem. B, 2014, 2, 6730 DOI: 10.1039/C4TB01153H

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