The Synergistic Effects of Multidrug-Loaded Nanocarriers Improve Tumor Microenvironment Responsive Chemo-Sonodynamic Therapy of Hepatocellular Carcinoma

摘要

Chemotherapy works synergistically with sonodynamic therapy in a multifunctionalsystem and is employed to improve the therapeutic outcomes ofhepatocellular carcinoma. In this study, ultrasound-responsive multi-functionalnanoparticles (USFNPs) are loaded with dual drugs, doxorubicin, and acomposite ultrasound-sensitive agent, curcumin-gold. The USFNPs are modifiedwith an acid-hydrolyzable polyethylene glycol outermost layer, making itstable in blood and normal tissues while peeling off in the acidic tumor microenvironment.The USFNPs have high specificity to liver tumor cells (Hepa1–6 cells); can escape from lysosomes following endocytosis, and exhibitbetter biocompatibility. Moreover, the carriers enhance the nuclear delivery ofthe drugs and inhibit p-glycoprotein (P-gp) expression of Hepa 1–6 cells. Incancer cells, carriers convert hydrogen peroxide into oxygen, improving thehypoxic microenvironment and generating abundant superoxide anion andhydroxyl radicals. Confocal laser scanning microscopy, 1H nuclear magneticresonance, flow cytometry, cytotoxicity, acute toxicity assays, and Western blotanalysis are used to demonstrate the results. The findings suggest USFNPsas novel and potential antitumor agents for treating hepatocellular carcinoma.