纳米剂型紫杉醇与 AZD9291 协同作用在体内根除非小细胞肺癌。
Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.
机构信息
Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan, University of Science & Technology, Luoyang 471003, China.
Department of Biochemistry & Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
出版信息
Nanomedicine (Lond). 2018 May;13(10):1107-1120. doi: 10.2217/nnm-2017-0355. Epub 2018 Jun 6.
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.
目的
本研究旨在开发针对 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
我们制备并表征了载紫杉醇和 AZD9291 的二硫键交联胶束（DCM），并评估了它们在体外和肺癌荷瘤小鼠中的联合作用和毒性。
结果
载药 DCM 粒径较小，具有谷胱甘肽响应性药物释放。PTX-DCMs 和 AZD92921-DCMs 的联合在细胞系和体内均表现出强烈的协同作用，而没有额外的毒性。分子研究表明，IKB-α/NF-κB/Bcl-2 和 EGFR/Akt 通路均有协同修饰。
结论
载 DCM 的 AZD9291 和 PTX 的联合应用可能为肺癌患者提供更有效、毒性更低的治疗选择。
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