Metal-organic framework decorated with glycyrrhetinic acid conjugated chitosan as a pH-responsive nanocarrier for targeted drug delivery

Stimulus-responsive nanomaterials have become a hot spot in controllable drug delivery systems researches owing to their spatiotemporal controllable properties based on the differences between tumor microenvironment and normal tissue. Herein, iron (III) carboxylate metal-organic framework nanoparticles coated with glycyrrhetinic acid-chitosan conjugate (MIL-101/GA-CS) were successfully fabricated and acted as the pH-responsive and target-selective system to deliver doxorubicin (DOX) for hepatocellular carcinoma (HCC) therapy. The prepared nanocarrier possess the advantages of uniform size, comparable drug loading efficiency (28.89%), and superior pH-dependent controlled drug release (DOX release of 2.74% and 89.18% within 72 h at pH 7.4 and 5.5, respectively). In vitro cytotoxicity assays showed that the drug-loaded nanocarriers exhibited excellent inhibitory effects on HepG2 cells due to the sustained release of DOX, while the nanocarriers showed no significant toxicity. Furthermore, cell uptake experiments demonstrated that MIL-101-DOX/GA-CS could target HepG2 cells based on receptor-dependent internalization of glycyrrhetinic acid receptors mediated. In vitro 3D hepatoma cell microspheres experiments showed that MIL-101-DOX/GA-CS had excellent penetration and tumor killing ability. Therefore, MIL-101-DOX/GA-CS nanoparticles have a prospective application in cancer therapy as a pH-responsive controlled drug delivery system.