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.

中文翻译：

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DNA 纳米机器人可作为癌症治疗剂，响应体内的分子触发。


纳米级机器人具有作为响应分子触发的智能药物输送系统的潜力。使用 DNA 折纸，我们构建了一个自主 DNA 机器人，该机器人被编程为运输有效载荷并将其专门呈现在肿瘤中。我们的纳米机器人的外部具有DNA适体，该适体结合核仁素（一种在肿瘤相关内皮细胞上特异性表达的蛋白质）以及其内腔内的凝血蛋白酶凝血酶。核仁素靶向适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。内部的凝血酶因此暴露并激活肿瘤部位的凝血。使用荷瘤小鼠模型，我们证明静脉注射 DNA 纳米机器人可将凝血酶特异性递送至肿瘤相关血管并诱导血管内血栓形成，从而导致肿瘤坏死并抑制肿瘤生长。该纳米机器人在小鼠和巴马小型猪中被证明是安全的且具有免疫惰性。我们的数据表明，DNA 纳米机器人代表了癌症治疗中精确药物输送的一种有前途的策略。