US-triggered ultra-sensitive "thrombus constructor" for precise tumor therapy.

ABSTRACT

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.