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.
Nanomedicine (Lond). 2018 May;13(10):1107-1120. doi: 10.2217/nnm-2017-0355. Epub 2018 Jun 6.
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.
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.
The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.
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。
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。
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。
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。
