Dual Loading of Nanoparticles with Doxorubicin and Icotinib for the Synergistic Suppression of Non-Small Cell Lung Cancer
Dual Loading of Nanoparticles with Doxorubicin and Icotinib for the Synergistic Suppression of Non-Small Cell Lung Cancer
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双负载阿霉素和埃克替尼纳米粒子协同抑制非小细胞肺癌
DOI：
10.7150/ijms.39172
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Zhou, Liansuo
中科院分区：
文献类型：
--
作者：
Li, Ke;Zhan, Wenhua;Zhou, Liansuo
背景：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不可逾越的障碍。方法：采用CCK-8法评价厄洛替尼（Erlotinib）、阿帕替尼（Apatinib）和埃克替尼（icotinib）与阿霉素（DOX）联合治疗NSCLC的最佳方案。然后将阳离子两亲性淀粉（CSaSt）和透明质酸（HA）共包封DOX和EGFR抑制剂，制备EDS纳米粒。结果：埃克替尼与阿霉素联合应用对肺癌细胞株A549、NCI-H1975、PC 9及肺癌小鼠移植瘤有较好的协同作用。随后，将埃克替尼和DOX共包封在NP中。EDS纳米颗粒大致为球形，平均尺寸为65.7 ± 6.2 nm，具有稳定的负载和释放性能。在体外研究中，EDS纳米颗粒可以有效地将有效载荷递送到细胞中，表现出细胞毒性并产生强的抗迁移特性。通过急性毒性和溶血试验证实了体内低毒性。体内分布表明，EDS纳米粒可增强肿瘤中的蓄积，减少正常器官中的非特异性蓄积。EDS NPs在小鼠模型中显著促进埃克替尼和DOX的体内协同效应。结论：该研究表明，EDS NPs具有值得注意的发展潜力，作为NSCLC临床化疗的治疗剂。
Background: 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.Methods: 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.Results: 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 in vitro investigation, EDS NPs could efficiently deliver payloads into cells, exhibited cytotoxicity and produced strong anti-migration properties. In vivo hypotoxicity was confirmed by acute toxicity and hemolytic assays. The in vivo distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the in vivo synergistic effects of icotinib and DOX in the mouse model.Conclusions: The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.