mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy

Journal of Nanobiotechnology

Research

Yan Zheng¹  Liang Zhao¹  Yijie Shi¹  Chang Su² 

[1] School of Pharmacy, Jinzhou Medical University, 121000, Jinzhou, People’s Republic of China;School of Veterinary Medicine, Jinzhou Medical University, 121000, Jinzhou, People’s Republic of China;

关键词: EGFR;    Tyrosine kinase inhibitor;    Nanoparticles;    Gefitinib;    Autophagy;    Chloroquine;   

DOI  :  10.1186/s12951-017-0302-5

 received in 2017-06-01, accepted in 2017-09-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundTyrosine kinase inhibitors (TKIs) that act against the epithelial growth factor receptor (EGFR) were once widely used in chemotherapy for many human cancers. However, acquired chemoresistance occurred in almost all patients, limiting the clinical application of EGFR-TKI. Thus far, no effective methods existing can resolve this problem. Designing a therapeutic treatment with a specific multi-target profile has been regarded as a possible strategy to overcome acquired EGFR-TKI resistance.MethodsMDR1 antibody-modified chitosan nanoparticles loading gefitinib and autophagy inhibitor chloroquine were prepared by ionic crosslinking and electrostatic attracting method. MTT assay, flow cytometry analysis and western blot assay were all performed to confirm the effect of different formulations of gefitinib on the proliferation of SMMC-7721/gefitinib cells. The preparations demonstrated their multi-target potential to achieve both tumor-targeting selectivity and the desired antitumor effects by blocking cell-surface MDR1 and inhibiting autophagy.ResultsmAb MDR1-modified CS NPs, when combined with the co-delivery of gefitinib and chloroquine, showed targeting and therapeutic potential on enhancing the delivery of anticancer drugs and inducing significant cell apoptosis against acquired EGFR-TKI resistance through the modulation of autophagy and while blocking the activity of the MDR1 receptor.ConclusionsA new approach to design an excellent nanoparticle drug-delivery system can overcome acquired EGFR-TKI resistance against various multiple antitumor targets.

【 授权许可】

CC BY   
© The Author(s) 2017