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

DNA origami-based nanorobot presents thrombin to cause tumor infarction after specific recognition of a tumor vessel marker. Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers 1 , 2 , 3 , 4 . Using DNA origami we constructed an autonomous DNA robo...

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Vydáno v:	Nature biotechnology Ročník 36; číslo 3; s. 258 - 264
Hlavní autoři:	Li, Suping, Jiang, Qiao, Liu, Shaoli, Zhang, Yinlong, Tian, Yanhua, Song, Chen, Wang, Jing, Zou, Yiguo, Anderson, Gregory J, Han, Jing-Yan, Chang, Yung, Liu, Yan, Zhang, Chen, Chen, Liang, Zhou, Guangbiao, Nie, Guangjun, Yan, Hao, Ding, Baoquan, Zhao, Yuliang
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.03.2018 Nature Publishing Group
Témata:	13/31 13/51 14/19 14/3 14/34 14/5 59/57 631/67/1059/602 631/67/327 639/301/357/341 639/925/926/1048 639/925/926/1050 64/110 64/60 82/29 Agriculture Animal models Animals Aptamers Aptamers, Nucleotide - administration & dosage Aptamers, Nucleotide - genetics Bioinformatics Biomedical Engineering/Biotechnology Biomedicine Biotechnology Blood coagulation Blood vessels Blood Vessels - drug effects Blood Vessels - growth & development Blood Vessels - pathology Cancer Cancer treatment Cell Proliferation - drug effects Coagulation Deoxyribonucleic acid DNA DNA - administration & dosage DNA - chemistry Drug delivery Drug Delivery Systems Endothelial cells Endothelial Cells - drug effects Endothelial Cells - pathology Humans letter Life Sciences Mice Nanoparticles Neoplasms - drug therapy Neoplasms - pathology Nucleolin Payloads Phosphoproteins - genetics Protein Binding RNA-Binding Proteins - genetics Swine Technology application Thrombin Thrombin - administration & dosage Thrombin - chemistry Thromboembolism Thrombosis Tumors Xenograft Model Antitumor Assays
ISSN:	1087-0156, 1546-1696, 1546-1696
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Shrnutí:	DNA origami-based nanorobot presents thrombin to cause tumor infarction after specific recognition of a tumor vessel marker. Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers 1 , 2 , 3 , 4 . 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 5 , 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1087-0156 1546-1696 1546-1696
DOI:	10.1038/nbt.4071