Supramolecular self-assembled DNA nanosystem for synergistic chemical and gene regulations on cancer cells.

Abstract

Incorporating multiple molecular interactions within a system to realize the metabolic reprogramming of cancer cells is prospected to be of great potential in cancer therapy. Herein, we report a supramolecular self-assembled DNA nanosystem, which reprogrammed the cellular antioxidant system via synergistic chemical and gene regulations. In the nanosystem, amphipathic telluroether was coordinated with Mn(II) to self-assemble into micelle, on which a siNrf2 integrated DNA network was assembled. The great electron-donating capability of telluroether was revealed to greatly promote Mn(II)-based Fenton-like reaction to generate subversive ·OH in cancer cells. In response to adenosine triphosphoric acid, the siNrf2 was specially released in cytoplasm for down-regulating expression of detoxification enzymes, which enhanced chemocatalysis-mediated oxidative stress in cancer cells, thus significantly suppressing tumor progression.