Superior antitumor effect of extremely high drug loading self-assembled paclitaxel nanofibers
Superior antitumor effect of extremely high drug loading self-assembled paclitaxel nanofibers
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极高载药量自组装紫杉醇纳米纤维的卓越抗肿瘤作用
DOI：
10.1016/j.ijpharm.2017.04.081
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发表时间：
2017-06-30
影响因子：
5.8
通讯作者：
Xie, Weiping
中科院分区：
文献类型：
--
作者：
Xu, Huae;Lu, Xiaowei;Xie, Weiping
为了克服紫杉醇的溶解度差和紫杉醇的超敏性，近年来的研究主要集中在紫杉醇（Ptx）的纳米递送系统上。尽管许多研究使用不同类型的聚合物作为载体制备了负载ptx的聚合物纳米颗粒，但负载ptx的聚合物纳米颗粒的负载效率相对较低，这极大地限制了其应用。本文设计并合成了一种简单的Ptx和琥珀酸偶联物（Ptx- sa），该材料可以自组装成纳米纤维，并以Ptx作为药物载体成为“无载体”。Ptx的最高加载效率为89.5%，呈可控释放模式。细胞摄取研究表明Ptx-SA纳米纤维被A549细胞内化。体外细胞毒性实验结果表明，Ptx- sa纳米纤维对A549细胞的抑制作用明显优于游离Ptx，特别是在较低的工作浓度下。克隆实验表明，与等剂量的游离Ptx相比，Ptx- sa对A549细胞克隆能力的改善作用增强。此外，与同等剂量的游离Ptx相比，Ptx- sa显著降低了p-Akt的表达，增加了裂解PARP和Caspase-3的表达，表明Ptx- sa的诱导凋亡作用增强。动物实验表明，与游离Ptx相比，Ptx- sa具有更好的抗肿瘤作用。因此，将Ptx与SA偶联可使负载Ptx的纳米纤维自组装，具有更强的体内体外抗肿瘤作用，是提高Ptx治疗肺癌疗效的一种有前景的方法。(C) 2017年Elsevier B.V.出版
Recent studies focused on the nanodelivery system of paclitaxel (Ptx) to overcome the poor solubility and hypersensitivity of Ptx caused by the application of Cremophor EL as a solvent. Although many studies use different types of polymers as carriers to prepare Ptx-loaded polymeric nanoparticles, the relatively low loading efficiency of Ptx-loaded polymeric nanoparticles significantly limits its application. Here, we design and synthesize a simple conjugation of Ptx and succinic acid (Ptx-SA), which can self-assemble into nanofibers and become "carrier-free" with Ptx as the drug carrier. The highest loading efficiency of Ptx is 89.5% with a controlled release pattern. The cellular uptake study indicates the internalization of Ptx-SA nanofibers by A549 cells. The in vitro cytotoxicity test results indicate that Ptx-SA nanofibers were much more effective in inhibiting the proliferation of A549 cells than free Ptx, particularly at the lower working concentration. The clonogenic assay shows the enhanced effect of Ptx-SA in ameliorating the clonogenic abilities of A549 cells compared with the equivalent dose of free Ptx. Moreover, Ptx-SA significantly attenuates the expression of p-Akt and increases the expression of cleaved PARP and Caspase-3 compared to the equivalent dose of free Ptx, which demonstrates the enhanced apoptosisinducing effect of Ptx-SA. The animal study demonstrates the superior antitumor effect of Ptx-SA compared to free Ptx. Therefore, the conjugation of Ptx with SA enables the self-assembly of Ptx-loaded nanofibers with stronger in vitro and in vivo antitumor effects, which is a promising method to improve the therapeutic efficacy of Ptx in treating lung cancer. (C) 2017 Published by Elsevier B.V.