Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Int J Biol Macromol. 2018 Jun;112:343-355. doi: 10.1016/j.ijbiomac.2018.01.195. Epub 2018 Jan 31.
Tumor metastasis is the primary obstacle in cancer treatment and is always the leading cause of human death. And heparin and its derivatives are potential anti-metastatic agents with good biocompatibility. In this work, low molecular weight heparin (LMWH) based LMWH-Cholesterol (LHC) conjugates were prepared for intravenous delivery of doxorubicin (DOX). The DOX/LHC nanoparticles (DOX/LHC NPs) exhibited a spherical shape with a mean diameter of 135.5±2.2nm and had a longer circulation time than that of DOX. The in vitro results confirmed that the DOX/LHC NPs was more effectively taken up by 4T1 cells and showed a stronger anti-metastatic effect by cell invasion and cell migration compared with DOX. Meanwhile, DOX/LHC NPs also exhibited superior anti-metastatic effects in the pulmonary metastasis model compared with other groups. The reason may be account for the synergistic effect between the cytotoxic drug of DOX and its drug carrier of LMWH based nanoparticles, which is capable of anti-metastatic and anti-angiogenic efficiency. Thus DOX/LHC nanoparticles could be a promising anti-metastatic drug delivery system for postoperative chemotherapy.
肿瘤转移是癌症治疗的主要障碍，也是导致人类死亡的主要原因。肝素及其衍生物是具有良好生物相容性的潜在抗转移药物。在这项工作中，制备了基于低分子量肝素（LMWH）的低分子量肝素-胆固醇（LHC）缀合物，用于阿霉素（DOX）的静脉给药。DOX/LHC 纳米颗粒（DOX/LHC NPs）呈球形，平均直径为 135.5±2.2nm，比 DOX 的循环时间更长。体外实验结果证实，DOX/LHC NPs 被 4T1 细胞摄取的效率更高，细胞侵袭和细胞迁移实验表明，与 DOX 相比，其具有更强的抗转移作用。同时，与其他组相比，DOX/LHC NPs 在肺转移模型中也表现出更好的抗转移效果。原因可能是 DOX 的细胞毒性药物与基于 LMWH 的纳米药物载体之间的协同作用，这种载体具有抗转移和抗血管生成的效率。因此，DOX/LHC 纳米颗粒可能是一种有前途的用于术后化疗的抗转移药物递送系统。
