AZD9291 Resistance Reversal Activity of a pH-Sensitive Nanocarrier Dual-Loaded with Chloroquine and FGFR1 Inhibitor in NSCLC.
AZD9291 Resistance Reversal Activity of a pH-Sensitive Nanocarrier Dual-Loaded with Chloroquine and FGFR1 Inhibitor in NSCLC.
复制标题
DOI：
10.1002/advs.202002922
复制
发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Gu Y;Lai S;Dong Y;Fu H;Song L;Chen T;Duan Y;Zhang Z
AZD9291 can effectively prolong survival of non‐small cell lung cancer (NSCLC) patients. Unfortunately, the mechanism of its acquired drug resistance is largely unknown. This study shows that autophagy and fibroblast growth factor receptor 1 signaling pathways are both activated in AZD9291 resistant NSCLC, and inhibition of them, respectively, by chloroquine (CQ) and PD173074 can synergistically reverse AZD9291 resistance. Herein, a coloaded CQ and PD173074 pH‐sensitive shell–core nanoparticles CP@NP‐cRGD is developed to reverse AZD9291 resistance in NSCLC. CP@NP‐cRGD has a high encapsulation rate and stability, and can effectively prevent the degradation of drugs in circulation process. CP@NP‐cRGD can target tumor cells by enhanced permeability and retention effect and the cRGD peptide. The pH‐sensitive CaP shell can realize lysosome escape and then release drugs successively. The combination of CP@NP‐cRGD and AZD9291 significantly induces a higher rate of apoptosis, more G0/G1 phase arrest, and reduces proliferation of resistant cell lines by downregulation of p‐ERK1/2 in vitro. CQ in CP@NP‐cRGD can block protective autophagy induced by both AZD9291 and PD173074. CP@NP‐cRGD combined with AZD9291 shows adequate tumor enrichment, low toxicity, and excellent antitumor effect in nude mice. It provides a novel multifunctional nanoparticle to overcome AZD9291 resistance for potential clinical applications. This work develops a coloaded chloroquine and fibroblast growth factor receptor 1 (FGFR1) inhibitor pH‐sensitive shell–core nanoparticles CP@NP‐cRGD, which can significantly dual‐block autophagy and FGFR1 pathway to overcome AZD9291 resistance. CP@NP‐cRGD can ensure excellent tumor targeting ability, realize lysosomal escaping, and release drugs sequentially by pH‐sensitive CaP shell. CP@NP‐cRGD has low toxicity and long circulation time in vivo.
登录
查看更多内容
影响因子：
5.6
作者：
Chen, Gaozhi;Bao, Yuyan;Liang, Guang
通讯作者：
Liang, Guang
AZD9291耐药非小细胞肺癌细胞系中环状RNA谱的综合分析
影响因子：
2.9
作者：
Chen, Tianxiang;Luo, Jizhuang;Yang, Yunhai
通讯作者：
Yang, Yunhai
影响因子：
5.6
作者：
Chude CI;Amaravadi RK
通讯作者：
Amaravadi RK
用于局部药物递送的热响应纳米复合凝胶通过诱导自噬抑制神经胶质瘤的生长
影响因子：
13.3
作者：
Ding, Li;Wang, Qi;Duan, Yourong
通讯作者：
Duan, Yourong
影响因子：
6.2
作者：
Jakobsen KR;Demuth C;Madsen AT;Hussmann D;Vad-Nielsen J;Nielsen AL;Sorensen BS
通讯作者：
Sorensen BS