Li Ke, Zhan Wenhua, Jia Min, Zhao Yufeng, Liu Yingguang, Jha Rajiv Kumar, Zhou Liansuo
Shaanxi Key Laboratory of Brain Disorders, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, 710021, Shaanxi, China.
Department of Radiotherapy, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia China.
Int J Med Sci. 2020 Feb 4;17(3):390-402. doi: 10.7150/ijms.39172. eCollection 2020.
: Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared. : Erlotinib, apatinib and icotinib were evaluated for optimal combination with DOX in treatment of NSCLC via CCK-8 assay. Then the cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were applied to coencapsulate DOX and EGFR inhibitor to form the EDS NPs. EDS NPs were evaluated in NSCLC cell lines (A549, NCI-H1975 and PC9) and NSCLC xenograft mouse models. : Icotinib was found to be the optimal synergistic drug in combination with DOX in the tested. Subsequently, icotinib and DOX were coencapsulated in the NPs. EDS NPs were roughly spherical with an average size of 65.7±6.2 nm and possessed stable loading and releasing properties. In the investigation, EDS NPs could efficiently deliver payloads into cells, exhibited cytotoxicity and produced strong anti-migration properties. hypotoxicity was confirmed by acute toxicity and hemolytic assays. The distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the synergistic effects of icotinib and DOX in the mouse model. : The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.
联合化疗在非小细胞肺癌（NSCLC）的临床治疗中发挥着重要作用。然而，药物之间的药代动力学差异是传统治疗中一个无法逾越的障碍。为了实现NSCLC的协同治疗，设计并制备了负载表皮生长因子受体（EGFR）抑制剂和阿霉素（DOX）的协同纳米颗粒（EDS NPs）。通过CCK-8试验评估了厄洛替尼、阿帕替尼和埃克替尼与DOX联合治疗NSCLC的最佳组合。然后应用阳离子两亲性淀粉（CSaSt）和透明质酸（HA）共同包裹DOX和EGFR抑制剂以形成EDS NPs。在NSCLC细胞系（A549、NCI-H1975和PC9）和NSCLC异种移植小鼠模型中对EDS NPs进行了评估。结果发现埃克替尼是测试中与DOX联合使用的最佳协同药物。随后，将埃克替尼和DOX共同包裹在纳米颗粒中。EDS NPs大致呈球形，平均粒径为65.7±6.2 nm，具有稳定的负载和释放特性。在研究中，EDS NPs能够有效地将有效载荷递送至细胞内，表现出细胞毒性并产生强大的抗迁移特性。急性毒性和溶血试验证实其低毒性。分布情况表明，EDS NPs能够增强在肿瘤中的蓄积并减少在正常器官中的非特异性蓄积。在小鼠模型中，EDS NPs显著促进了埃克替尼和DOX的协同作用。该研究表明，EDS NPs作为NSCLC临床化疗的治疗药物具有值得关注的开发潜力。
