Graphene quantum dots-crosslinked gelatin via the efficient Ugi four-component reaction: Safe photoluminescent implantable carriers for the pH-responsive delivery of doxorubicin

In this work, citric acid-based graphene quantum dots (GQDs) were used for crosslinking gelatin (G) via the Ugi four-component reaction (Ugi-4CR) with different ratios of Ugi-4CR reactants ratios as an innovative facile, green, and straightforward method. The synthesized GQDs-crosslinked gelatin (GQD-G) hydrogels were analyzed by XRD, FT-IR, NMR, PL, SEM, and Zeta potential techniques. To explain the productivity of synthesized hydrogels as a pH-responsive drug delivery system, doxorubicin (DOX) as a model anticancer drug was loaded into them through the soaking in drug solution. The results of in-vitro swelling and drug release studies revealed dependency on the time, pH, and degree of Ugi-4CR crosslinking. GQD-G hydrogel with 0.25 mmol Ugi-4CR reactant exhibited a higher pH responsivity. It was showed a low release rate at simulated physiological environmental (pH 7.4, 37°C), but it is raised at tumor tissue conditions (pH 4.5, 41°C), extending and sustaining the delivery of DOX. Importantly, by raising the Ugi-4CR-crosslinked contents, the MTT assay exhibits a good cytocompatibility and significant cytotoxicity against breast cancer cell line (MCF-7) for the blank and DOX-loaded GQD-G, respectively. From the obtained results, the synthesized cytocompatible photoluminescent GQD-G hydrogels with suitable pH responsivity have the potential to be utilized as an implantable anticancer and bio-detection agent. © 2021