Editors' ChoiceNanotechnology

Tumor-hunting nanorobots

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Science Translational Medicine  28 Feb 2018:
Vol. 10, Issue 430, eaas8968
DOI: 10.1126/scitranslmed.aas8968

Abstract

A DNA nanorobot kills tumors by blocking the blood supply.

Solid tumors often develop an abnormal, excessive vasculature to meet the demand for nutrients and oxygen for cancer cell survival and growth. Blocking tumor vasculature is thus an attractive therapeutic strategy to starve tumor cells. However, it is critical that such a therapy could distinguish and block tumor blood vessels without affecting those in healthy tissues. Here, Li et al. offer a solution with a “smart,” tumor-hunting nanorobot design that uses DNA origami and encapsulated thrombin. The DNA robots selectively trigger intravascular thrombosis (blood clotting) in tumors, resulting in necrosis and inhibition of tumor growth in mouse models.

The authors designed a nanorobot consisting of a DNA origami nanotube self-assembled from a rectangular DNA origami sheet, with thrombin molecules attached and shielded on the inner side. The nanotube is “zipped” with fastener strands containing DNA aptamers that recognize nucleolin proteins selectively expressed by tumor vasculature. Upon reaching the target, the nanotube is “unzipped” back to a sheet to expose thrombin molecules, which induce blood coagulation. The researchers first characterized the structure and configuration of the thrombin-functionalized nanorobots. They confirmed the catalytic activity of thrombin in the nanorobot, the closed and open states of the nanorobot, and the recognition of cell-surface nucleolin by the fastener strands. The authors then showed that the fasteners could dissociate upon binding to recombinant or endothelial-expressed nucleolin, which in turn exposed the encapsulated thrombin within the nanorobots to cause blood coagulation. Nanorobots injected into tumor-bearing mice accumulated in tumor vasculature but were cleared from normal organs. They further demonstrated advanced thrombosis in tumor vessels and inhibition of tumor growth in mouse models of breast cancer, melanoma, lung, and ovarian cancer. The authors evaluated the safety of the nanorobot system and showed there was no cytotoxicity in cell cultures, nor observable thrombi in the cerebral microcirculation or evidence of an inflammatory immune response in mice. Last, the safety of nanorobots was confirmed in Bama miniature pigs, which resemble human anatomy and physiology.

Overall, Li et al. demonstrated that the DNA nanorobot system can achieve targeted delivery of therapeutic thrombin in tumor blood vessels, blocking tumor blood supply and inhibiting tumor growth without safety concerns. The technology has the potential to treat not only primary tumors but also metastases. However, although the nanorobot-treated tumor-bearing animals in the study showed improved survival, they still succumbed to the cancer—which makes it necessary to explore combinatorial options to further improve the efficacy.

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