Inhibition of cancer-associated thrombosis with redox-sensitive paclitaxel/heparin-deoxycholic acid nanoparticles
Inhibition of cancer-associated thrombosis with redox-sensitive paclitaxel/heparin-deoxycholic acid nanoparticles
复制标题
氧化还原敏感的紫杉醇/肝素-去氧胆酸纳米颗粒抑制癌症相关血栓形成
DOI：
10.1016/j.colcom.2020.100345
复制
发表时间：
2021-01-01
影响因子：
4.5
通讯作者：
Yin, Jinghua
中科院分区：
文献类型：
--
作者：
Ke, Yue;Cui, Lele;Yin, Jinghua
虽然肝素纳米粒被广泛用于治疗癌症，但肝素衍生物和肝素纳米粒对癌症相关血栓形成的影响仍然缺乏了解。为了解决这一问题，合成了具有非敏感性（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，并将紫杉醇（PTX）封装在肝素基胶束中以制备纳米粒。对合成的聚合物的化学结构、纳米粒子的尺寸、形貌、稳定性以及氧化还原敏感性进行了分析。并在体内外研究了肝素-脱氧胆酸聚合物和紫杉醇纳米粒对肿瘤相关血栓形成的影响。发现氧化还原敏感的PTX/纳米颗粒有效地减少癌症小鼠的血栓形成。这一结果主要归因于癌细胞凋亡后凝血功能下调。这项工作不仅阐明了肝素基纳米颗粒对血液高凝状态的影响，而且提供了抑制癌症相关血栓形成的基本原理。
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.