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Coordinative Amphiphiles as Tunable siRNA Transporters. | LitMetric

Coordinative Amphiphiles as Tunable siRNA Transporters.

Bioconjug Chem

Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.

Published: August 2016

AI Article Synopsis

  • The study focuses on developing new amphiphiles as siRNA transporters by using a modified cationic lipid structure that incorporates a zinc(II)-dipicolylamine complex for improved binding to siRNAs.
  • These amphiphiles are easy to synthesize and modify, and they not only bind to siRNA but also protect it from degradation by enzymes like RNase A.
  • The research shows that combining different membrane-directing groups with the zinc complex can enhance siRNA delivery efficiency while minimizing cytotoxicity, allowing for tunable uptake pathways based on the chosen group.

Article Abstract

In this study, we developed coordinative amphiphiles for use as novel siRNA transporters. As a modification of a conventional cationic lipid structure, we replaced the cationic head with zinc(II)-dipicolylamine complex (Zn/DPA) as a phosphate-directing group, and used various membrane-directing groups in the place of the hydrophobic tails. These simple amphiphiles are readily synthesized and easy to modify. The Zn/DPA head groups bind to the phosphate backbones of siRNAs, and to our surprise, they prevented the enzymatic degradation of siRNAs by RNase A. Interestingly, the Zn/DPA head itself exhibited moderate transfection efficiency, and its combination with a membrane-directing group-oleoyl (CA1), pyrenebutyryl (CA2), or biotin (CA3)-enhanced the delivery efficiency without imparting significant cytotoxicity. Notably, the uptake pathway was tunable depending on the nature of the membrane-directing group. CA1 delivered siRNAs mainly through caveolae-mediated endocytosis, and CA2 through clathrin- and caveolin-independent endocytosis; CA3 recruited siRNAs specifically into biotin receptor-positive HepG2 cells through receptor-mediated endocytosis. Thus, it appears possible to develop tunable siRNA transporters simply by changing the membrane-directing parts. These are the first examples of amphiphilic siRNA transporters accompanying coordinative interactions between the amphiphiles and siRNAs.

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Source
http://dx.doi.org/10.1021/acs.bioconjchem.6b00260DOI Listing

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