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DNA nanorobots with dynamic mechanisms also have great potential for use in intelligent drug delivery systems that respond to target molecules [116]. Programmed DNA origami structures that respond to specific molecules were designed to be effective for tumor recognition [117]. A nanorobot was functionalized with an exterior DNA aptamer that binds to a protein specifically expressed on tumor‐associated endothelial cells and the blood coagulation protease thrombin on the interior. The aptamer functions as a lock for the DNA nanorobot to open mechanically. When the nanorobot opens, the thrombin inside is exposed and promotes blood clotting at the tumor site. Using a mouse model, the DNA nanorobot was introduced into the blood and delivered thrombin specifically to the tumor‐associated blood vessel, induced tumor necrosis, and inhibited tumor growth. In addition, the nanorobot was immunologically inactive in vivo. This demonstrates that the strategy to use target selective DNA nanorobots is promising for accurate drug delivery and cancer therapy.

Figure 1.16 A DNA nanorobot that recognizes cells. Schematic drawings of the closed nanorobot in hexagonal barrel shape loaded with protein payloads inside in front view. Antibodies are introduced into the tubular shape and is closed by the “key” DNA strand (dashed square). Mechanism for opening the “key.” The target molecule (circle) binds to the upper DNA strand (aptamer DNA) and the initial dsDNA is dissociated. Schematic view of the open state of the nanorobot by protein key displacement of aptamer locks. When the nanorobot is in the open state, antibodies inside bind to cell‐specific antigens.

Source: Douglas et al. [115]/with permission of American Association for the Advancement of Science.