AKT1 and cancer: Notably, the combined therapy demonstrated a significant 14-fold increase in cytotoxicity against HER2+ metastatic cancer cells (SK-OV-3) in comparison to GEM used alone, which was further proved mechanistically that GEM@PLGA@HM operated synergistically to hinder the progression and metastasis of HER2+ tumors by triggering apoptosis and concurrently inhibiting the PI3K/AKT and MAPK signaling cascades.