Abstract
<title>Abstract</title> <p>Hepatocellular carcinoma (HCC) is a globally prevalent malignancy with limited therapeutic options and dismal prognosis, highlighting an urgent need for novel agents and delivery strategies. Lupiwighteone, a natural prenylated isoflavone with potent anticancer properties, is severely hampered in clinical translation by its poor aqueous solubility and undefined mechanism against HCC. Reactive oxygen species (ROS) are critical redox regulators involved in cancer progression, and autophagy represents an attractive programmed cell death for cancer intervention. In this study, lupiwighteone suppressed HCC malignant phenotypes by inhibit EGFR/MAPK/mTOR signaling pathway to induce ROS-dependent autophagy. To address lupiwighteone’s pharmaceutical defects, we constructed biomimetic nanoparticles loaded with lupiwighteone and cloaked with Hep3B cell membranes (CCMNP@Lup). Comprehensive physicochemical characterization and biological evaluation verified that CCMNP@Lup markedly elevated lupiwighteone solubility, bioavailability, and homologous tumor targeting capacity, thereby achieving strengthened anti HCC efficacy. Collectively, this study provides a feasible biomimetic nanotherapeutic strategy for HCC management and lays pre-clinical groundwork for lupiwighteone based HCC treatment.</p>