title: Crosslinked Redox-Responsive Micelles Based on Lipoic Acid-Derived Amphiphiles for Enhanced siRNA Delivery.
abstract: Successful application of gene silencing approaches critically depends on systems that are able to safely and efficiently deliver genetic material such as small interfering RNA (siRNA). Due to their beneficial well-defined dendritic nanostructure, self-assembling dendrimers are emerging as promising nanovectors for siRNA delivery. However, these kinds of vectors are plagued with stability issues, especially when considered for in vivo applications. Therefore, in the present study, disulfide-based temporarily fixed micelles are developed that can degrade upon reductive conditions, and thus lead to efficient cargo release. In detail, lipoic acid-derived crosslinked micelles are synthesized based on small polymerizable dendritic amphiphiles. Particularly, one candidate out of this series is able to efficiently release siRNA due to its redox-responsive biodegradable profile when exposed to simulated intracellular environments. As a result, the reduction-triggered disassembly leads to potent gene silencing. In contrast, noncrosslinkable, structurally related constructs fails under the tested assay conditions, thereby confirming the applied rational design approach and demonstrating its large potential for future in vivo applications.
authors: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors: Ariane
authors: A
authors: Tschiche
authors: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors: Bala N S
authors: BN
authors: Thota
authors: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors: Falko
authors: F
authors: Neumann
authors: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors: Andreas
authors: A
authors: Schäfer
authors: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors: Nan
authors: N
authors: Ma
authors: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors: Rainer
authors: R
authors: Haag
mesh_terms: D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D008823:Micelles; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry; D008063:Thioctic Acid / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D050091:Dendrimers; D008823:Micelles; D034741:RNA, Small Interfering; D013501:Surface-Active Agents; D008063:Thioctic Acid
keywords: bio-responsive; crosslinking; dendritic amphiphiles; gene transfection; siRNA delivery