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Nat Biotechnol. 2018 Mar;36(3):258-264. doi: 10.1038/nbt.4071. Epub 2018 Feb 12.

A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo.

Author information

1
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, China, Beijing, China.
2
University of Chinese Academy of Sciences, Beijing, China.
3
College of Pharmaceutical Science, Jilin University, Changchun, China.
4
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
5
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
6
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China.
7
School of Molecular Sciences, Center for Molecular Design and Biomimetics; School of Life Sciences, Center for Immunotherapy, Vaccines, and Virotherapy at the Biodesign Institute, Arizona State University, Tempe, Arizona, USA.
8
Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
9
Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.

Abstract

Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.

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PMID:
29431737
DOI:
10.1038/nbt.4071
[Indexed for MEDLINE]

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