A unique highly hydrophobic anticancer prodrug self-assembled nanomedicine for cancer therapy
A unique highly hydrophobic anticancer prodrug self-assembled nanomedicine for cancer therapy
复制标题
一种独特的高疏水性抗癌前药自组装纳米药物，用于癌症治疗
DOI：
10.1016/j.nano.2016.06.012
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发表时间：
2016-11-01
影响因子：
5.4
通讯作者：
He, Zhonggui
中科院分区：
文献类型：
--
作者：
Ren, Guolian;Jiang, Mengjuan;He, Zhonggui
与通常的想法相反，我们产生了高度疏水性的抗癌前药自组装纳米粒子没有表面活性物质的帮助下，基于多西他赛的共轭D-α-生育酚琥珀酸酯。还原敏感的前药合成与二硫键插入到连接体中，并与对照还原不敏感的前药进行比较。研究了自组装纳米粒子的形貌和稳定性。细胞毒性和细胞凋亡实验表明，还原敏感型纳米粒比还原不敏感型纳米粒具有更高的抗癌活性。与含多西他赛吐温80的制剂和还原不敏感的纳米粒相比，还原敏感的纳米粒表现出良好的体内抗肿瘤活性和耐受性。总之，独特的纳米药物表现出许多优点：（i）制备的容易性和再现性，（ii）高药物有效载荷，（iii）上级稳定性，（iv）延长循环，和（v）改善治疗效果。这种高度可重复的分子组装策略将推动新纳米医学的发展。(C)2016 Elsevier Inc. All rights reserved.
In contrast with common thought, we generated highly hydrophobic anticancer prodrug self-assembled nanoparticles without the aid of surface active substances, based on the conjugation of docetaxel to D-a-tocopherol succinate. The reduction-sensitive prodrug was synthesized with a disulfide bond inserted into the linker and was compared with a control reduction-insensitive prodrug. The morphology and stability of self-assembled nanoparticles were investigated. Cytotoxicity and apoptosis assays showed that the reduction-sensitive nanoparticles had higher anticancer activity than the reduction-insensitive nanoparticles. The reduction-sensitive nanoparticles exhibited favorable in vivo antitumor activity and tolerance compared with docetaxel Tween80-containing formulation and the reduction-insensitive nanoparticles. Taken together, the unique nanomedicine demonstrated a number of advantages: (i) ease and reproducibility of preparation, (ii) high drug payload, (iii) superior stability, (iv) prolonged circulation, and (v) improved therapeutic effect. This highly reproducible molecular assembly strategy should motivate the development of new nanomedicines. (C) 2016 Elsevier Inc. All rights reserved.