Abstract:Like normal organs, tumors need to establish a blood supply to satisfy their demand for oxygen and nutri­ents and accomplish other metabolic functions. However, tumor vessels display considerable variation in the patterning and properties, as well as in their responses to vessel targeted therapy. Based on the potential vulnerabilities that could be targeted in vascular system, we developed several nanorobotic drugs to selectively infarct tumor vessels or modulate microenvironmental components to achieve safe and effective antitumor therapy. For achieving targeted tumor vessel occlusion, we have designed an autonomous, tubular DNA nanorobots capable of specifically binding to the tumor vascular endothelium and presenting the coagulation protease thrombin to locally induce tumor infarction and necrosis. We also developed the intelligent polymer and peptide nanodrugs that deplete intratumoral platelets, dramatically enhancing the permeability of tumor vessels and thus stimulating the accumulation of chemotherapeutic drugs within tumor tissues. With this seminal work in the development of nanorobot based anticancer therapeutics, it may be asserted that ‘swallowing the doctor’ may not be too far away.