Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy
Co-delivery of doxorubicin and paclitaxel by reduction/pH dual responsive nanocarriers for osteosarcoma therapy
复制标题
通过还原/pH双响应纳米载体共同递送阿霉素和紫杉醇用于骨肉瘤治疗
DOI：
10.1080/10717544.2020.1785049
复制
发表时间：
2020-01-01
期刊：
影响因子：
6
通讯作者：
Zhang, Zhiyu
中科院分区：
文献类型：
--
作者：
Li, Yongshuang;Hou, Hao;Zhang, Zhiyu
基于纳米颗粒的给药系统为癌症联合治疗提供了一个很有前景的平台。然而，细胞内药物释放效率低，降低了肿瘤纳米药物的治疗效果。本文制备了聚乙二醇化聚硫辛酸共聚物（mPEG-P α - LA），并将其作为还原/pH双响应纳米载体，同时递送紫杉醇（PTX）和阿霉素（DOX）用于骨肉瘤治疗。两亲性mPEG-P α LA在水溶液自组装过程中可以有效地封装PTX和DOX，从而生成PTX和DOX共载纳米粒子（NP-PTX-DOX）。制备的NP-PTX-DOX在还原性和酸性刺激下显示出增强的PTX和DOX释放。此外，通过流式细胞术分析和激光共聚焦扫描显微镜证实，双药负载纳米颗粒被K7骨肉瘤细胞有效内化，并在细胞内释放药物。因此，NP-PTX-DOX在K7细胞中表现出协同治疗作用并诱导细胞凋亡增强。此外，与对照组相比，NP-PTX-DOX在小鼠骨肉瘤模型中表现出更好的生物分布和更高的肿瘤生长抑制功效。总之，这项工作的结果表明，所提出的策略是有希望的骨肉瘤治疗使用mPEG-P α - LA共聚物作为双重反应的纳米载体，共同递送抗癌药物。
Nanoparticle-based drug delivery system offers a promising platform for combination cancer therapy. However, the inefficient drug release in cells reduces the therapeutic efficacy of cancer nanomedicines. Herein, a PEGylated poly(alpha-lipoic acid) copolymer (mPEG-P alpha LA) was prepared and used as a reduction/pH dual responsive nanocarrier to simultaneously deliver paclitaxel (PTX) and doxorubicin (DOX) for osteosarcoma therapy. The amphiphilic mPEG-P alpha LA could efficiently encapsulate both PTX and DOX during its self-assembly into micelles in aqueous solution to generate PTX and DOX co-loaded nanoparticles (NP-PTX-DOX). The as-prepared NP-PTX-DOX showed enhanced PTX and DOX release in response to reductive and acidic stimuli. Moreover, the dual-drug loaded nanoparticles were efficiently internalized by K7 osteosarcoma cells and released drugs intracellularly, as confirmed by flow cytometry analysis and confocal laser scanning microscopy. Consequently, NP-PTX-DOX exhibited synergistic therapeutic effects and induced enhanced cell apoptosis in K7 cells. Furthermore, NP-PTX-DOX presented improved biodistribution and higher tumor growth inhibition efficacy compared to the control groups in a murine osteosarcoma model. Altogether, the results of this work indicate that the proposed strategy is promising for osteosarcoma therapy using mPEG-P alpha LA copolymer as a dual-responsive nanocarrier to co-deliver anticancer drugs.