Metal-organic framework/carboxymethyl starch/graphene quantum dots ternary hybrid as a pH sensitive anticancer drug carrier for co-delivery of curcumin and doxorubicin

• For the first time, a new Bio-MOF(Zn)@CMS/GQDs nanovehicle was fabricated. • DOX and CUR loaded on Bio-MOF(Zn)@CMS/GQDs (DOX@CUR@Bio-MOF(Zn)@CMS/GQDs). • DOX@CUR@Bio-MOF(Zn)@CMS/GQDs effectively released the drugs in simulated tumor tissues. • DOX@CUR@Bio-MOF(Zn)@CMS/GQDs showed enhanced anti-tumor efficacy than DOX@CUR. • DOX@CUR@Bio-MOF(Zn)@CMS/GQDs effectively transported the DOX and CUR to the nucleus and killed the HepG2 cancer cells. • Overall, from the application and components point of view, synthesized Bio-MOF(Zn)@CMS/GQDs in this work is a new structure with novelty. The efficiency of graphene quantum dots (GQDs) and glutamic acid-based metal-organic framework (Bio-MOF(Zn)) compounds have been reported in the drug delivery area. In addition, carboxymethyl starch (CMS) has a good performance in improving biocompatibility and obtaining a controlled anticancer drug release system. Fabrication of Bio-MOF(Zn)@CMS/GQDs can be hopeful in cancer treatment. In this work for the first time, a novel pH-sensitive and biocompatible drug carrier was prepared with the combination of CMS, GQDs, and Bio-MOF(Zn) for curcumin (CUR) and doxorubicin (DOX) co-delivery. For this, GQDs were prepared via pyrolysis of citric acid (CA). Then the CMS and GQDs mixture was crosslinked with zinc metal (Zn-CMS/GQDs). Finally, the Bio-MOF(Zn) was simply fabricated in the presence of L-glutamic acid (Glu) as proteinogenic amino acid and Zn-CMS/GQDs as a biocompatible platform (Bio-MOF(Zn)@CMS/GQDs). The formation of zinc-glutamate Bio-MOF in the presence of Zn-CMS/GQDs was elucidated by the common characterization techniques. Brunauer-Emmett-Teller (BET) analysis obtained the pore diameter of Bio-MOF(Zn)@CMS/GQDs ternary hybrid at about 4.5 nm. The in vitro drug loading test obtained the loading percentage of CUR and DOX at about 54.2% and 43.2%. Moreover, the pH-sensitive drug release behavior was observed. Cellular tests confirmed the biocompatibility of Bio-MOF(Zn)@CMS/GQDs and its capability for cancer cell treatment after drug loading. A Survey of the published research works shows that the studied Bio-MOF(Zn)@CMS/GQDs as a DOX and CUR co-carrier have novelty from both components and application viewpoints. In conclusion, the obtained results can render the Bio-MOF(Zn)@CMS/GQDs ternary hybrid as a newly introduced smart candidate for anticancer drug delivery with great potential in biomedicine.