Surface engineering of graphene as a novel nano-carrier for doxorubicin using sugar-based deep eutectic systems

The future of graphene as a drug nano-carrier lies in nanotechnolgy where it can be tailor-made to favor the cellular biological environment. Therefore, an innovative route was implemented to improve the biocompatibility of graphene using binary and ternary sugar-based deep eutectic systems (DESs) as green functionalizing agents with composition of choline chloride (ChCl):glucose (2:1), ChCl:fructose (2:1), ChCl:fructose:water (5:2:5), and ChCl:glucose:water (5:2:5). The changes in physicochemical properties of sugar-based DES-functionalized graphene were observed via FESEM, FTIR, BET, XRD, and Raman spectroscopy, testifying the addition of DES-functional groups. The biocompatibility of graphene was significantly improved post functionalization with sugar-based ternary DES compared to sugar-based binary DES as validated in biological assays. The ternary DES-functionalized graphene demonstrated higher doxorubicin (DOX) loading capacity as compared to the binary DES-functionalized graphene. To gain molecular-level insights, computational simulations via quantum chemical calculations were performed to elucidate the interactions between graphene, DES components, and DOX. After DOX loading, the graphene exhibited damaging impacts against cancerous cells through the intracellular ROS production and cell cycle disruption phenomena. Real-time cell growth analysis was further investigated to confirm the cytotoxicity kinetic response of DOX loaded-Gr against cancerous cells over time. The results of this cellular kinetic response were in accordance with the DOX loading capacity data. Sugar-based ternary DESs, ChCl:glucose:water and ChCl:fructose:water, were the most promising functionalizing agents for nano-drug carriers, owing to their lower cytotoxicity, higher drug loading capacity, and significant inhibition of the cancer cell growth profile.