ULK1 Mediated Autophagy-Promoting Effects of Rutin-Loaded Chitosan Nanoparticles Contribute to the Activation of NF-κB Signaling Besides Inhibiting EMT in Hep3B Hepatoma Cells

• DOI: 10.2147/ijn.s443117
• Publication Date: 2024-05-18T10:35:12Z
• Authors: Peng Wu; Xiaoyong Wang; Min Yin; Wenjie Zhu; Zheng Chen; Yang Zhang; Ziyu Jiang; Longqing Shi; Qiang Zhu
• Keywords: ULK1

Background: Liver cancer remains to be one of the leading causes worldwide. The treatment options face several challenges and nanomaterials have proven improve bioavailability drug candidates their applications in nanomedicine. Specifically, chitosan nanoparticles (CNPs) are extremely biodegradable, pose enhanced biocompatibility considered safe for use medicine. Methods: CNPs were synthesized by ionic gelation, loaded with rutin (rCNPs) characterized ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared (FTIR), dynamic light scattering (DLS) transmission electron microscopy (TEM). rCNPs tested cytotoxic effects on human hepatoma Hep3B cells, experiments conducted determine mechanism such effects. Further, was L929 fibroblasts, hemocompatibility determined. Results: Initially, UV–vis FTIR analyses indicated possible loading rCNPs. load quantitatively measured using Ultra-Performance Liquid Chromatography (UPLC) concentration 88 μg/mL 0.22 micron filtered capacity (LC%) observed 13.29 ± 0.68%, encapsulation efficiency (EE%) 19.55 1.01%. release pH-responsive as 88.58% released after 24 hrs at lysosomal pH 5.5, whereas 91.44% physiological 7.4 102 hrs. prominent samples 5 mg/mL precursor. particle size this 144.1 nm polydispersity index (PDI) 0.244, which is deemed ideal tumor targeting. A zeta potential (ζ-potential) value 16.4 mV good stability. IC 50 cells 9.7 0.19 load. In addition, increased production reactive oxygen species (ROS) changes mitochondrial membrane (MMP) observed. Gene expression studies that due activation Unc-51-like autophagy-activating kinase (ULK1) mediated autophagy nuclear factor kappa B (NF-κB) signaling besides inhibiting epithelial–mesenchymal Transition (EMT). less toxic NCTC clone 929 (L929) fibroblasts comparison possessed excellent (less than 2% hemolysis). Conclusion: physicochemical properties suitable particles effectively normal hemocompatibility. very low hemolytic profile indicates could administered intravenously therapy. Keywords: rCNPs, Hep3B, ROS, qPCR,