Multifunctional luteolin-Fe@PVA microspheres for combined hepatocellular carcinoma treatment: Embolization/sonodynamic/chemodynamic therapy

Transarterial embolization (TAE) is a primary clinical treatment for hepatocellular carcinoma (HCC); however, its therapeutic efficacy is limited by its functional constraints. To enhance treatment outcomes, this study aims to develop a multifunctional embolic microsphere, LUT-Fe@PVA, for the combined treatment of HCC. This approach leverages a synergistic strategy that integrates TAE, sonodynamic therapy (SDT), and chemodynamic therapy (CDT) to improve the therapeutic efficacy. The LUT-Fe@PVA microspheres were synthesized via a microemulsion crosslinking method and loaded with luteolin-iron complexes to enable ultrasound-triggered reactive oxygen species (ROS) generation and Fenton reaction for enhanced tumor destruction. In vitro results demonstrated that the combination therapy significantly kills the tumor cells. In vivo, 18 F-FDG microPET/CT imaging revealed significantly reduced uptake values, while histological analysis confirmed extensive tumor cell necrosis and apoptosis in the combined therapy group. This study presents a promising multifunctional approach for HCC treatment by integrating embolization, SDT, and CDT, offering a novel strategy for effective and selective tumor treatment with minimal side effects.