Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin–fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy.

由于肿瘤从幸存的肿瘤边缘组织再生长，因此在肿瘤血管系统中引起血栓形成的药物并未导致长期根除肿瘤，肿瘤细胞可以从相邻的非肿瘤血管和组织中获取营养。在这里，我们报道了通过基于壳聚糖的纳米颗粒进行的肿瘤梗塞治疗和化学疗法的结合，所述纳米颗粒装饰有针对肿瘤血管壁和肿瘤基质中过表达的针对纤维蛋白-纤连蛋白复合物的肿瘤归巢肽，并包裹了凝血诱导性蛋白酶凝血酶和化学疗法阿霉素。与仅递送凝血酶或阿霉素的纳米颗粒相比，将纳米颗粒全身性施用于患有皮下或原位肿瘤的小鼠和兔子可导致更高的肿瘤生长抑制和更低的肿瘤复发，并且组织学和血液学分析表明没有可检测到的毒性。与可生物降解的靶向肿瘤的纳米颗粒共同施用细胞毒性有效载荷和蛋白酶以引发肿瘤中的血管梗塞代表了一种改善基于凝血的肿瘤治疗指标的有前途的策略。