Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance.
Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance.
复制标题
西妥昔单抗修饰介孔二氧化硅纳米药物特异性靶向EGFR突变肺癌并克服耐药性
DOI：
10.1038/srep25468
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发表时间：
2016-05-06
影响因子：
4.6
通讯作者：
Ji H
中科院分区：
文献类型：
--
作者：
Wang Y;Huang HY;Yang L;Zhang Z;Ji H
对酪氨酸激酶抑制剂（TKI）的耐药是表皮生长因子受体（EGFR）突变型肺癌患者有效治疗的主要障碍。在这里，我们设计了西妥昔单抗封端的介孔二氧化硅纳米粒子（MP-SiO2 NP）作为药物载体，以特异性靶向EGFR突变型肺癌细胞，并有效地释放负载的药物，包括阿霉素和吉非替尼。这种创新的纳米药物可以特异性地靶向EGFR高表达的肺癌细胞，而不是EGFR水平低的肺癌细胞。用负载吉非替尼的西妥昔单抗封端的MP-SiO2 NP处理衍生自PC 9细胞的吉非替尼抗性细胞系（PC 9-DR）显示出对细胞生长的显著抑制。此外，这种纳米药物成功地抑制了PC 9-DR异种移植肿瘤的进展。这种肿瘤抑制是由于大量纳米药物的内吞作用和高谷胱甘肽（GSH）水平诱导的PC 9-DR细胞中吉非替尼的有效释放。总的来说，我们的研究提供了一种使用西妥昔单抗修饰的MP-SiO2 NP克服EGFR-TKI耐药性的新方法，该方法具有有效管理EGFR突变型肺癌的强大潜力。
Drug resistance to tyrosine kinase inhibitor (TKI) is the main obstacle for efficient treatment of epidermal growth factor receptor (EGFR)-mutant lung cancer patients. Here we design a cetuximab-capped mesoporous silica nanoparticle (MP-SiO2NP) as the drug carrier to specifically target EGFR-mutant lung cancer cells and efficiently release loaded drugs including doxorubicin and gefitinib. This innovative nano-medicine can specifically target lung cancer cells with high EGFR expression rather than those with low EGFR level. Treatment of a gefitinib-resistant cell line derived from PC9 cell (PC9-DR) with the gefitinib-loaded cetuximab-capped MP-SiO2NP showed a significant inhibition of cell growth. Moreover, this nano-medicine successfully suppressed the progression of PC9-DR xenograft tumors. This tumor suppression was due to the endocytosis of large amount of nano-medicine and the effective gefitinib release induced by high glutathione (GSH) level in PC9-DR cells. Collectively, our study provides a novel approach to overcome EGFR-TKI resistance using cetuximab modified MP-SiO2NP, which holds strong potential for effective management of EGFR-mutant lung cancer.