Interactions of IOX1, a histone demethylase inhibitor, with essential metal ions, albumin, and its clay-based nanoformulation

) (RhCp*) complex of IOX1 was synthesized and characterized by UV-visible, NMR, and mass spectrometry techniques, showing high stability in aqueous solution without the dissociation of IOX1 over a wide pH range and strong interaction with human serum albumin. To access the potential benefits of nanocapsulation, IOX1-loaded anionic clay (LDH) nanoparticles (LDH/IOX1) were successfully synthesized. The anticancer properties of IOX1, its RhCp* complex, and LDH/IOX1 were evaluated in human cancer cell lines. The RhCp* complex exhibited a greater antiproliferative activity toward Colo205 cells than IOX1 alone, and all tested compounds significantly decreased the mitochondrial membrane potential. The LDH/IOX1 system also showed pronounced cytotoxicity on A549 cells, accompanied by strong mitochondrial impairment, indicating the potential of nanocapsulation of small-molecule enzyme inhibitors in cancer therapy.