Alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles for active mitochondrial targeting and...

The ability of some tumours to impart radioresistance serves as a barrier in the cancer therapeutics. Mitochondrial metabolism significantly persuades this cancer cell survival, incursion and plays a crucial role in conferring radioresistance. It would be of great importance to target the active mitochondria to overcome this resistance and achieve tumoricidal efficacy. The current report investigates the improved radiosensitization effect (under Gamma irradiation) in hepatocellular carcinoma through active mitochondrial targeting of alpha-ketoglutarate decorated iron oxide-gold core-shell nanoparticles (GNP). The loading of a chemotherapeutic drug N-(4-hydroxyphenyl)retinamide in GNP allows adjuvant chemotherapy, which further sensitizes cancerous cells for radiotherapy. The GNP shows a drug loading efficiency of 8.5 wt% with a sustained drug release kinetics. The X-Ray diffraction (XRD) pattern and High-Resolution Transmission Electron microscopy (HRTEM) indicates the synthesis of core iron oxide nanoparticles with indications of a thin layer of gold shell on the surface with 1:7 ratios of Fe: Au. The GNP application significantly reduced per cent cell viability in Hepatocellular carcinoma cells through improved radiosensitization at 5 Gy gamma radiation dose. The molecular mechanism revealed a sharp increment in reactive oxygen species (ROS) generation and DNA fragmentation. The mitochondrial targeting probes confirm the presence of GNP in the mitochondria, which could be the possible reason for such improved cellular damage. In addition to the active mitochondrial targeting, the currently fabricated nanoparticles work as a potent Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) contrast agent. This multifunctional therapeutic potential makes GNP as one of the most promising theragnostic molecules in cancer therapeutics.