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.