Preparation of a pH-responsive chitosan-montmorillonite-nitrogen-doped carbon quantum dots nanocarrier for attenuating doxorubicin limitations in cancer therapy

Abstract

Despite its widespread usage as a chemotherapy drug in cancer treatment, doxorubicin (DOX) has limitations such as short in vivo circulation time, low solubility, and poor permeability. In this regard, a pH-responsive chitosan (CS)- montmorillonite (MMT)- nitrogen-doped carbon quantum dots (NCQDs) nanocomposite was first developed, loaded with DOX, and then incorporated into a double emulsion to further develop the sustained release. The incorporated NCQDs into the CS-MMT hydrogel exhibited enhanced loading and entrapment efficiencies. The presence of NCQDs nanoparticles in the CS-MMT hydrogel also resulted in an extended pH-responsive release of DOX over a period of 96 h compared to that of CS-MMT-DOX nanocarriers at pH 5.4. Based on the Korsmeyer-Peppas model, there was a controlled DOX release at pH 5.4, while no diffusion was observed at pH 7.4, indicating fewer side effects. MTT assay showed that the cytotoxicity of DOX-loaded CS-MMT-NCQDs hydrogel nanocomposite was significantly higher than those of free DOX (p < 0.001) and CS-MMT-NCQDs (p < 0.001) on MCF-7 cells. Flow cytometry results demonstrated that a higher apoptosis induction achieved after incorporating NCQDs nanoparticles into CS-MMT-DOX nanocarrier. These findings suggest that the DOX-loaded nanocomposite is a promising candidate for the targeted treatment of cancer cells.