Although heparin-based nanoparticles are widely used to treat cancer, the knowledge on the effect of heparin derivative and heparin-based nanoparticles on cancer-associated thrombosis is still lacking. To address this issue, the heparin derivatives including amphiphilic heparin-deoxycholic acid (DOCA) polymer with non-sensitive (Hep-DOCA) and redox-sensitive properties (Hep-ss-DOCA) are synthesized, and paclitaxel (PTX) is encapsulated in heparin-based micelles to fabricate nanoparticles. The chemical structure of synthesized polymer, the size, morphology and stability of nanoparticles and redox-sensitivity of nanoparticles are analyzed. And the effect of heparin-deoxycholic acid polymer and PTX loaded nanoparticles on cancer-associated thrombosis are investigated both in vitro and in vivo. It is found that redox-sensitive PTX/nanoparticles is effectively in reducing thrombosis for cancer mice. This result is mainly attributed to down-regulation for coagulation after apoptosis of cancer cell. This work not only clarifies the effect of heparin-based nanoparticles on blood hypercoagulation but provides basic principles to inhibit cancer-associated thrombosis.

尽管基于肝素的纳米颗粒被广泛用于治疗癌症，但仍缺乏关于肝素衍生物和基于肝素的纳米颗粒对与癌症相关的血栓形成的作用的知识。为了解决这个问题，合成了包括具有非敏感性（Hep-DOCA）和氧化还原敏感性（Hep-ss-DOCA）的两亲性肝素-脱氧胆酸（DOCA）聚合物的肝素衍生物，并将紫杉醇（PTX）封装在基于肝素的胶束可制造纳米颗粒。分析了合成聚合物的化学结构，纳米粒子的尺寸，形态和稳定性以及纳米粒子的氧化还原敏感性。并在体内和体外研究了肝素-脱氧胆酸聚合物和负载PTX的纳米颗粒对癌症相关血栓形成的影响。发现氧化还原敏感的PTX /纳米颗粒可有效减少癌症小鼠的血栓形成。该结果主要归因于癌细胞凋亡后凝血的下调。这项工作不仅阐明了基于肝素的纳米颗粒对血液高凝的影响，而且提供了抑制癌症相关血栓形成的基本原理。