Zhang, W.-B.* DNA Nano-robot: What Dreams May Come. Acta Polym. Sin. 2021, 52, 335-338.

Nano-robots that are capable of entering the human body to cure disease and save life have been a science fiction and a futuristic therapeutic dream. Recently, Baoquan Ding’s group and Guangjun Nie’s group at the National Center for Nanoscience and Technology have made considerable progress in this direction with the development of a DNA nanodevice-based vaccine for cancer immunotherapy. A tubular DNA nanostructure was designed and prepared by first forming a DNA rectanglevia DNA origami, precise loading of an antigen and two types of molecular adjuvants, and subsequent tube-closing by low pH-responsive DNA “locking strands” on the edge. When injected subcutaneously, this DNA nanodevice can be delivered efficiently to the draining lymph nodes and accumulates in lysosomes within the antigen-presenting cells. The local acidic subcellular environment triggers the release of the DNA locking strands to expose the vaccine and elicit a potent antigen-specific T-cell response, leading to significant tumor regression and inhibition of tumor reoccurrence in mouse cancer models. Impressively, they also demonstrate strong long-term memory effect of this vaccine against tumor rechallenge. All these features indicate that this DNA nanodevice provides a platform for precise and programmable delivery of molecular medicines. It is a milestone toward fulfilling the dream of the “nanorobot doctor” proposed by Feynman some seventy years ago and holds great promise to transform modern medicine and medical care.