Construction of chitooligosaccharide-based nanoparticles of pH/redox cascade responsive for co-loading cyclosporin A and AZD9291. (1st September 2022)

• Record Type: Journal Article
• Authors: Chen, Shumin; Ji, Xiaoguo; Zhao, Mengyao; Jin, Jiayang; Zhang, Haiping; Zhao, Liming
• Is Part Of: Carbohydrate polymers. Volume 291(2022)
• Publication Date: 2022-09-01
• Subjects: COS chitooligosaccharide -- CsA Cyclosporin A -- NSCLC non-small cell lung cancer -- EGFR epidermal growth factor receptor -- TKI tyrosine kinase inhibitors -- FDA U.S. Food and Drug Administration -- NCCN the National Comprehensive Cancer Network -- NDDS nano-drug delivery system -- NPs nanoparticles -- EPR enhancing permeability and retention effect -- GSH glutathione -- DEE drug encapsulation efficiency -- DLE drug loading efficiency -- HPLC high-performance liquid chromatography -- FTIR Fourier transform infrared spectroscopy -- PDI polydispersity index -- FM fluorescence microscopy -- FC flow cytometry -- PARP poly ADP-ribose polymerase; Chitooligosaccharides -- Drug delivery system -- AZD9291 -- Cyclosporin A -- Nanoparticles; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2022.119619
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: 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. Graphical abstract: Unlabelled Image