Dual Action Against Gastric Cancer: Iron Oxide Nanoparticles Conjugated With Juglone and Hyaluronic Acid Induce Apoptosis and Modulate Oncogenic Genes

ABSTRACT

Gastric cancer (GC) remains a leading cause of cancer mortality because of late diagnosis, limited therapeutic selectivity, and drug resistance. This study developed a multifunctional iron oxide nanoparticle delivery system conjugated with Juglone and hyaluronic acid (Fe ₃ O ₄ @C‐HA‐Juglone) to improve gastrointestinal bioavailability, selectively target GC cells, trigger apoptosis, and regulate oncogenic gene expression. Nanoparticles were characterized by DLS, zeta potential, FESEM, TEM, EDS, FT‐IR, TGA, XRD, and VSM. They showed a hydrodynamic diameter of approximately 551 nm and a zeta potential of −46.9 mV, indicating colloidal stability and suitability for cellular uptake. Morphological and structural analyses confirmed spherical core–shell particles with successful Juglone and HA conjugation, while superparamagnetic behavior and thermal stability supported targeted, sustained delivery. MTT assays demonstrated dose‐ and time‐dependent antiproliferative activity in AGS cells, with 24 and 48 h IC ₅₀ values of 56 and 29 µg/mL versus 162 µg/mL in normal cells at 24 h. Flow cytometry, ROS measurement, and AO/PI staining confirmed apoptosis and oxidative stress, accompanied by significant downregulation of ANRIL and HOXA11‐AS to 0.77‐ and 0.64‐fold. Overall, Fe ₃ O ₄ @C‐HA‐Juglone represents a selective nanotherapeutic platform with promising translational potential for GC treatment through combined magnetic targeting, HA receptor recognition, sustained release, selectivity, and molecular modulation mechanisms.