期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/srep25468
关键词
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资金
- National Basic Research Programm of China [2012CB910800]
- National Natural Science Foundation of China [81572949, 31500696, 81430066, 81402276, 81402371, 81401898, 81402498, 81372509, 31370747, 81325015]
- Science and Technology Commission of Shanghai Municipality [15XD1504000]
- cross and cooperation in science and technology innovation team program
- Shanghai Institutes for Biological Sciences [2014KIP304]
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-SiO2 NP) as the drug carrier to specifically target EGFRmutant 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-SiO2 NP 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-SiO2 NP, which holds strong potential for effective management of EGFR-mutant lung cancer.
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