癌症相关血栓（CAT）是癌症患者的常见并发症，显着影响他们的生活质量和生存前景。纳豆激酶 (NK) 具有有效的溶栓特性，但其功效因口服生物利用度低以及静脉使用时存在严重过敏反应的风险而受到限制。肝素（HP）是临床上广泛使用的抗凝剂。本研究旨在克服NK的静脉毒性，探讨其对晚期肿瘤CAT的作用。本研究构建了NK-HP静电复合物，并通过豚鼠过敏试验、小鼠尾静脉试验验证了其安全性和溶栓功效。 ，以及体内和体外溶栓实验。此外，还建立了S180晚期肿瘤模型，并与唾液酸修饰的阿霉素脂质体（DOX-SAL）联合，研究NK-HP对CAT的影响及其在晚期肿瘤中的抗肿瘤作用。我们观察到NK-HP可以消除静脉注射NK无毒性，具有较强的溶栓性能，并能阻止血栓形成。静脉注射NK-HP可通过降低晚期肿瘤中的纤维蛋白含量、增加交联蛋白降解产物D-二聚体的水平来增强DOX-SAL的抗肿瘤作用。本研究开发了一种消除静脉注射毒性的方法NK 提出了一种有前途的 CAT 治疗策略，特别是针对晚期肿瘤中的 CAT，并提高了纳米制剂在抗肿瘤治疗中的功效。版权所有 © 2024。由 Elsevier Inc. 出版。

Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors.In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors.We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer.This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy.Copyright © 2024. Published by Elsevier Inc.