Grapefruit-derived EVs, alongside those from C. paradisi, exhibited strong cytotoxicity against tumor cells, especially A375 melanoma cells, resulting in substantial viability reduction, cell cycle arrest, the downregulation of phosphorylated ERK and AKT, and a decrease in key mediators (ICAM1 and cathepsin) associated with cancer progression. The gene discussed is ICAM1; the disease is neoplasm.