Supramolecular Self‐Assembled DNA Nanosystem for Synergistic Chemical and Gene Regulations on Cancer Cells

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 MnII 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 MnII‐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.