Anticancer Activities of Tumor-killing Nanorobots

doi:10.1016/j.tibtech.2019.01.010

Trends in Biotechnology

Volume 37, Issue 6, June 2019, Pages 573-577

https://doi.org/10.1016/j.tibtech.2019.01.010 Get rights and content

Pharmaceutical uses of cancer therapeutics, such as intravenous thrombin to elicit blood coagulation, have been hampered by lack of tumor specificity. Based on rapid progress in DNA origami-based machines capable of transporting molecular payloads, DNA nanorobots have been constructed to specifically deliver therapeutic agents into tumor vessels.

Section snippets

Biological Activities and Therapeutic Application of Thrombin

Thrombin is a key enzyme in the blood coagulation cascade. As the main effector protease, thrombin cleaves plasma fibrinogen into fibrin monomers [1], which can spontaneously form insoluble polymers. Thrombin also activates the clotting factors VIII (to VIIIa) and V (to Va) and activates platelets. Together, these hemostasis mechanisms form thrombi that comprise platelet plugs and the self-polymerizing fibrin network [2]. Thrombin’s action is not confined to the coagulation event: it also has a

DNA Nanorobot-based Thrombin Delivery to Tumor Vessels

The DNA origami technique was introduced by Rothemund in 2006. A desired DNA origami structure is constructed by a long scaffold single-stranded DNA molecule folded into an arbitrary architecture using hundreds of staple strands that fix the scaffold’s conformation 5, 6, 7. The DNA origami method enables a rational design and production of DNA nanostructures with well-defined homogenous geometries, precise spatial addressability, and marked biocompatibility. DNA origami is a blank slate that

Advantages of DNA Nanorobot-based Tumor Infarction Therapy

The induction of tumor vascular infarction is considered one of the most efficient ways to inhibit tumor growth due to the abundance of capillaries associated with tumor angiogenesis and the prothrombotic state of tumors [13]. Moreover, as an acute blood event, vessel infarction requires a much shorter duration of treatment than many other therapies, and there is less possibility of developing drug resistance. In addition, cutting off the tumor blood supply elicits a potentiation effect since a

Future Perspectives

Thrombin has a central role in blood coagulation and represents a fascinating class of topical hemostatic drugs. However, thrombin’s utility typically suffers from fast degradation of the protein by proteases present in serum, with a half-life of only 25 s [1]. Moreover, potent procoagulant activity severely hampers intravenous applications of thrombin, limiting the range of diseases for which the drug may be applied in clinical settings. A recently developed tube-shaped DNA origami

Acknowledgments

This work was supported by grants from the National Key R&D Program of China (2018YFA0208900, 2016YFA0201601), the National Natural Science Foundation of China (31730032, 81871489, 31661130152, 31700871, and 21573051), Beijing Nova Program Interdisciplinary Cooperation Project (Z181100006218136), Beijing Municipal Science and Technology Commission (Z161100000116036), Key Research Program of Frontier Sciences, CAS (QYZDB-SSW-SLH029), and the CAS Interdisciplinary Innovation Team.

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Trends in Biotechnology

ForumAnticancer Activities of Tumor-killing Nanorobots

Section snippets

Biological Activities and Therapeutic Application of Thrombin

DNA Nanorobot-based Thrombin Delivery to Tumor Vessels

Advantages of DNA Nanorobot-based Tumor Infarction Therapy

Future Perspectives

Acknowledgments

Thrombin signalling and protease-activated receptors

Nature

Advances and innovations in haemophilia treatment

Nat. Rev. Drug Discov.

Hemostatic drugs

N. Engl. J. Med.

A review of the therapeutic uses of thrombin

Thromb. Haemost.

Folding DNA to create nanoscale shapes and patterns

Nature

DNA origami: fold, stick, and beyond

Nanoscale

DNA origami: scaffolds for creating higher order structures

Chem. Rev.

Forum
Anticancer Activities of Tumor-killing Nanorobots