Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.
Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.
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DOI：
10.2217/nnm-2017-0355
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发表时间：
2018-05
期刊：
影响因子：
5.5
通讯作者：
Xinshuai Wang;Li Zhang;Xiaocen Li;De-jiu Kong;Xiao-chen Hu;Xue-zhen Ding;Jun-qiang Yang;M. Zhao;Yixuan He;K. Lam;Shenshuo Gao;Tzu-Yin Lin;Yuanpei Li
中科院分区：
文献类型：
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作者：
Xinshuai Wang;Li Zhang;Xiaocen Li;De-jiu Kong;Xiao-chen Hu;Xue-zhen Ding;Jun-qiang Yang;M. Zhao;Yixuan He;K. Lam;Shenshuo Gao;Tzu-Yin Lin;Yuanpei Li
目的本研究旨在开发EGFR T790M靶向抑制剂AZD9291和紫杉醇（PTX）的新型纳米制剂，用于肺癌的联合治疗。材料与方法我们制备并表征了负载 PTX 和 AZD9291 的二硫键交联胶束 (DCM)，并在体外和肺癌小鼠中评估了它们的组合效果和毒性。结果载药DCM尺寸相对较小，并且具有谷胱甘肽响应性药物释放。 PTX-DCM 和 AZD92921-DCM 的组合在细胞系和体内表现出强大的协同作用，且没有额外的毒性。分子研究证明了 IKB-α/NF-κB/Bcl-2 和 EGFR/Akt 通路的协同修饰。结论 负载 DCM 的 AZD9291 和 PTX 的组合可能为肺癌患者提供更有效、毒性更小的治疗选择。
AIM This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer. MATERIALS & METHODS We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice. RESULTS Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways. CONCLUSION The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.