Mitochondria-Targeted Delivery of siRNA by Amphiphilic Nanovectors Self-Assembled from a Cationic [4]Helicene-Squalene Ester.

The active delivery of therapeutic nucleic acids with subcellular precision is an open challenge. Herein, a small conjugate molecule, combining a cationic [4]helicene moiety with a lipophilic squalene tail, yields amphiphilic nanoassemblies capable of effectively complexing siRNA within the mitochondria. A proof-of-concept in HCT 116 colorectal cancer cells was evidenced by Western blot for the delivery of siRNA silencing the protein expression of the mitochondria-encoded cytochrome c oxidase subunit 1 gene.