Folic acid-functionalized cerium oxide nanoparticles as smart nanocarrier for pH-responsive and targeted delivery of Morin in breast cancer therapy

Nanoceria (CeO2NP) has emerged as a promising carrier for effective delivery of various anticancer drugs. Herein, folic acid (FA) conjugated and amine-functionalized CeO2NPs (CeO2-NH-FA) have been synthesized for targeted and controlled delivery of Morin (a natural flavonoid) towards folic acid overexpressed breast cancer cells. Morin was successfully loaded onto the surface of CeO2-NH-FA via metal ion-ligand coordination bonds to form Morin-CeO2-NH-FA nanohybrids. The as synthesized nanohybrid exhibited nearly spherical shape with an average diameter of ∼ 2–3 nm. Moreover, the nanohybrid displayed drug loading content of ∼ 10 % along with pH-responsive drug release behaviour. The nanohybrids exhibited significant cytotoxic effect towards human breast cancer (MCF-7) cells via the generation of intracellular reactive oxygen species (ROS) which subsequently induced mitochondria-dependent apoptotic cell death. In addition, the nanohybrids also triggered potential anti-migratory effect. The in vivo results also revealed the highest anticancer effect of the Morin-CeO2-NH-FA nanohybrids in tumor-bearing mice as compared with free Morin and CeO2-NH-FA. Furthermore, Morin-CeO2-NH-FA nanohybrid did not show any significant change in serum biochemical parameters. To gain possible mechanistic pathway, we carried out molecular docking study of Morin with Bcl-2 protein which revealed that Morin can bind to Bcl-2 with an affinity of −7.1 kCal/mol. The pronounced anticancer effect of the nanohybrid towards breast cancer cells is mainly ascribed to the combined cytotoxic effect of both Morin as well as nanoceria. Overall, our study represents Morin-CeO2-NH-FA nanohybrid as a potential drug delivery vehicle with improved therapeutic efficacy against cancer.