Ferrite/curcumin hybrid nanocomposite formulation: Physicochemical characterization, anticancer activity, and apoptotic and cell cycle analyses in skin cancer cells

Abstract Skin cancer requires effective treatment due to its high incidence and mortality. Curcumin’s anti-tumor effects are restricted by its lower bioavailability, dose dependency, and poor skin permeability. Hybrid curcumin molecules with spinal metal ferrite and biogenic silver/silver chloride (Ag/AgCl) nanoparticles could be a promising approach for the efficient delivery of curcumin to cancer cells. AgClM 0.5 Fe 2 O 4 and AgClM 0.5 Fe 2 O 4 /curcumin hybrid nanocomposites were synthesized via chemical co-precipitation and wet impregnation techniques. Furthermore, they were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), dynamic light scattering (DLS), and vibrating sample magnetometry (VSM). The cytotoxicity, apoptosis, and cell cycling of hybrid nanocomposites were evaluated on human epidermoid skin carcinoma (A-431) and human skin fibroblast (HSF) cell lines. Results showed successful curcumin loading, high physical stability, and enhanced magnetic properties of the hybrid nanocomposites. Cytotoxicity assays revealed selective toxicity against both A-431 and HSF cell lines with IC₅₀ values of 26.83 and 34.83 µg/ml for AgClCd 0.5 Fe 2 O 4 and AgClMg 0.5 Fe 2 O 4 /curcumin, respectively. AgClCd 0.5 Fe 2 O 4 /curcumin exhibited greater apoptosis induction (14.52% late apoptosis, 8.53% necrosis) compared to AgClMg 0.5 Fe 2 O 4 /curcumin (10.20% late apoptosis, 6.07% necrosis). In addition, cell cycle analysis showed a significant increase in the sub-G1 phase, with AgClCd 0.5 Fe 2 O 4 /curcumin demonstrating superior efficacy. In conclusion, hybrid nanocomposites triggered cell cycle arrest and apoptosis, with AgClCd 0.5 Fe₂O₄/curcumin being the most potent. Their lower toxicity compared to doxorubicin suggests their potential application in skin cancer treatment.