Dual anticancer drug delivery of D-galactose-functionalized stimuli-responsive nanogels for targeted therapy of the liver hepatocellular carcinoma

[Display omitted] •D-galactose was used as a natural-based agent for CQDs synthesis.•The stimuli-responsive CQDs/β-CD/NIPAM@AA-Gal nanogels were synthesized in water solvent.•CQDs/β-CD/NIPAM@AA-Gal nanogels loaded with DOX@MTX and evaluated for drug delivery.•The CQDs/β-CD/NIPAM@AA-Gal nanogels displayed good cytocompatibility.•Internalization of the fabricated nanogels in the liver hepatocellular carcinoma was confirmed. In the current research work for the first time, we designed and fabricated a new double-responsive (pH and temperature) and photoluminescent nanogels capped with D-galactose (D-Gal) moieties (CQDs/β-CD/NIPAM@AA-Gal) in three steps and then evaluated its potential as a targeted drug carrier. The used common characterization techniques approved the success in fabrication of the CQDs/β-CD/NIPAM@AA-Gal nanogels. CQDs/β-CD/NIPAM@AA-Gal nanogels demonstrated homogeneous size distribution with an average hydrodynamic diameter of about 657 nm. About 47.8% and 72% of loading capacity respectively were observed respectively for methotrexate (MTX) and doxorubicin (DOX) anticancer drugs (MTX@DOX@CQDs/β-CD/NIPAM@AA-Gal). The controlled drug release ability of the MTX@DOX@CQDs/β-CD/NIPAM@AA-Gal was verified through a comparison of the drug release profiles at the simulated tumor and physiological conditions. In vitro cytotoxicity, 4′,6-diamidino-2-phenylindole (DAPI) staining, and cell cycle assays displayed the good biocompatibility of CQDs/β-CD/NIPAM@AA-Gal. Furthermore, fluorescent imaging approved its bioimaging potential. Overall summation of the achieved results proposes that the CQDs/β-CD/NIPAM@AA-Gal can be generally tested as a medical nanovehicle with a wide range of applicability potential for cancer cells monitoring and co-drug delivery.