Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer  

作　　者：Zi-tong Zhao Jue Wang Lei Fang Xin-di Qian Ying Cai Hai-qiang Cao Guan-ru Wang Mei-lin He Yan-yan Jiang Dang-ge Wang Ya-ping Li 

机构地区：[1]School of Pharmacy,Fudan University,Shanghai,201203,China [2]State Key Laboratory of Drug Research&Center of Pharmaceutics,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [3]Yantai Key Laboratory of Nanomedicine&Advanced Preparations,Yantai Institute of Materia Medica,Yantai,264000,China [4]Shandong Laboratory of Yantai Drug Discovery,Bohai Rim Advanced Research Institute for Drug Discovery,Yantai,264000,China [5]School of Pharmacy,Yantai University,Yantai,264005,China

出　　处：《Acta Pharmacologica Sinica》2023年第1期244-254,共11页中国药理学报（英文版）

基　　金：Financial support from the National Natural Science Foundation of China (81903548,32170935,32070927,81690265,31930066 and 82172615);the Youth Innovation Promotion Association of CAS (2019283);the Shanghai Sailing Program (19YF1457300);Shandong Provincial Natural Science Foundation (ZR2019PH013)are gratefully acknowledged.

摘　　要：The combination of vascular endothelial growth factor(VEGF)inhibitors and tyrosine kinase inhibitors(TKIs)is newly available for molecular targeted therapy against non-small cell lung cancer(NSCLC)in clinic.However,the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest.In this study,we developed bevacizumab-coated gefitinib-loaded nanoparticles(BCGN)with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor(EGFR).Through an exogenous corona strategy,bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction.After intravenous injection,BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging.Bevacizumab is released from BCGN upon oxidation in tumor microenvironment,whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm.The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models.Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

关 键 词：NANOPARTICLES molecular targeted therapy non-small cell lung cancer dual-responsive controlled release 

分 类 号：R73[医药卫生—肿瘤]