Embolization therapy is an attractive strategy for antitumor therapy, especially for solid tumors. In vivo self-coagulation behavior holds great potential in a new type of tumor embolization therapy. However, spatiotemporal controllable in situ formation of thrombus in tumor is a challenge. Herein, an ultrasound (US)-responsive ultra-sensitive "thrombus constructor" (UUNC), which was prepared by loading thrombin into a nanobubble, and modified with NGR peptide on its surface, is rational designed for tumor embolization therapy. Benefiting from the targeting ability of NGR peptides to tumor neovascularization, UUNC efficiently enriched in tumor vessels, and then released thrombin rapidly to form thrombi in situ of tumor blood vessels in the presence of US. In vivo antitumor experiments demonstrated that UUNC could significantly lead to tumor cell apoptosis and necrosis, and the tumor growth inhibition rate (TGI) was 85.3% with a transient US in tumor, while maintain high stability, and no obvious thrombus was observed in normal tissues. UUNC holds an attractive potential for tumor embolization therapy via spatiotemporal controllable thrombus construct strategy.

中文翻译：

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美国触发的超灵敏“血栓构建器”，用于精确的肿瘤治疗。

栓塞治疗是抗肿瘤治疗（尤其是实体瘤）的一种有吸引力的策略。体内自凝行为在新型肿瘤栓塞治疗中具有巨大潜力。然而，肿瘤中血栓的时空可控原位形成是一个挑战。本文中，针对肿瘤栓塞治疗的合理设计是通过将凝血酶加载到纳米气泡中并在其表面上用NGR肽修饰而制备的对超声（US）敏感的超灵敏“血栓构建体”（UUNC）。得益于NGR肽对肿瘤新血管形成的靶向能力，UUNC有效地富集了肿瘤血管，然后在存在US的情况下迅速释放了凝血酶，从而在肿瘤血管中原位形成了血栓。体内抗肿瘤实验表明，UUNC可以明显导致肿瘤细胞凋亡和坏死，在短暂的US中，肿瘤生长抑制率（TGI）为85.3％，同时保持较高的稳定性，在正常组织中未观察到明显的血栓。通过时空可控的血栓构建策略，UUNC在肿瘤栓塞治疗方面具有诱人的潜力。