A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo
A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo
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DNA 纳米机器人响应体内分子触发信号发挥癌症治疗作用
DOI：
10.1038/nbt.4071
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发表时间：
2018-03-01
影响因子：
46.9
通讯作者：
Zhao, Yuliang
中科院分区：
文献类型：
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作者：
Li, Suping;Jiang, Qiao;Zhao, Yuliang
纳米级机器人有潜力成为对分子触发作出反应的智能药物输送系统。利用DNA折纸技术，我们构建了一个自主的DNA机器人，通过编程来运输有效载荷，并将它们特异地呈现在肿瘤中。我们的纳米机器人在外部具有DNA适体的功能，该适体结合了核蛋白（一种在肿瘤相关内皮细胞上特异性表达的蛋白质）和其内腔内的凝血蛋白酶凝血酶。核蛋白靶向适配体既作为靶向结构域，又作为DNA纳米机器人机械打开的分子触发器。因此，内部的凝血酶暴露并激活肿瘤部位的凝血。利用荷瘤小鼠模型，我们证明了静脉注射DNA纳米机器人将凝血酶特异性地递送到肿瘤相关血管，并诱导血管内血栓形成，导致肿瘤坏死和肿瘤生长抑制。这种纳米机器人在老鼠和巴马迷你猪身上被证明是安全的，并且具有免疫惰性。我们的数据表明，DNA纳米机器人代表了一种很有前途的策略，可以在癌症治疗中精确地给药。
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.