文献类型：期刊文献

英文题名：Construction of chitooligosaccharide-based nanoparticles of pH/redox cascade responsive for co-loading cyclosporin A and AZD9291

作者：Chen, Shumin[1];Ji, Xiaoguo[1];Zhao, Mengyao[1,3];Jin, Jiayang[1,3];Zhang, Haiping[2];Zhao, Liming[1,3,4]

机构：[1]East China Univ Sci & Technol, R&D Ctr Separation& Extract Technol Fermentat Ind, Sch Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Tongji Univ, Shanghai Pulm Hosp, Dept Oncol, Sch Med, Shanghai 200092, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg Technol SCI, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Sch Biotechnol, Shanghai, Peoples R China

年份：2022

卷号：291

外文期刊名：CARBOHYDRATE POLYMERS

收录：;EI(收录号：20222112143155);WOS:【SCI-EXPANDED(收录号:WOS:000805838300001)】；

基金：Acknowledgments This work was supported by the National Key R&D Program of China (2019YFD0901800) , the Open Project Funding of the State Key Labo-ratory of Bioreactor Engineering, ECUST (ZDXM2019) , the Fundamental Research Funds for the Central Universities, and the 111 Project (B18022) .

语种：英文

外文关键词：Chitooligosaccharides; Drug delivery system; AZD9291; Cyclosporin A; Nanoparticles

摘要：AZD9291 can prolong the survival of patients with non-small cell lung cancer. Unfortunately, resistance to AZD9291 is inevitable and hinders effectiveness. Studies showed the combination of Cyclosporin A (CsA) and AZD9291 could increase the efficacy of AZD9291, but the delivery efficiency of free drugs was limited. A chitooligosaccharide (COS) -based nanoparticle with enhanced delivery efficiency and endocytosis was constructed in this study. The results showed that this pH/redox cascade responsive nanoparticles improved therapeutic effect. The system is small and the surface charge changed from negative to positive according to the weakly acidic tumor microenvironment. After endocytosis, the nanoparticles decomposed and released AZD9291 and CsA in redox-rich cytoplasm. Experiments in vitro and in vivo proved that the nanoparticles overcame the biological barrier and significantly enhanced the anti-tumor effect of AZD9291. The novel multifunctional nanoparticle provides a way to overcome the drug resistance and the possibility of clinical application.