Construction of Multifunctional Fe3O4@MSN@PDA-HA-FA Nanocarriers and Research on Synergistic Tumor Therapy

<b>Background:</b> Chemodynamic therapy (CDT) and photothermal therapy (PTT) based on nanomaterials have garnered widespread attention in cancer treatment. However, most single-modal nanotherapeutics suffer from limited therapeutic efficacy. <b>Methods:</b> Herein, a magnetic mesoporous composite nanoparticle, Fe₃O₄@MSN@PDA-HA-FA, is successfully fabricated, with Fe₃O₄ nanoparticles as the magnetic core; mesoporous silica nanoparticles (MSNs) as the mesoporous shell; and dopamine hydrochloride (DA·HCl), hyaluronic acid (HA), and folic acid (FA) as the functional ligands. <b>Results:</b> Notably, this composite serves as both an efficient photothermal converter and a chemodynamic promoter, enhancing hydroxyl radical (·OH) generation and improving PTT efficacy. Under near-infrared (NIR) light irradiation, Fe₃O₄@MSN@PDA-HA-FA exhibits high photothermal conversion and heat transfer efficiencies. The Fe²⁺ ions in Fe₃O₄ enable a Fenton reaction-mediated conversion of endogenous hydrogen peroxide (H₂O₂) into ·OH for CDT. Additionally, the MSNs provide a substantial drug-loading capacity, while the HA and FA provide additional surface functionalities that can modulate the nano-bio interactions and improve colloidal stability. <b>Conclusions</b>: In vitro experiments validate the synergistic therapeutic efficacy of PTT, CDT, and chemotherapy. This study demonstrates that Fe₃O₄@MSN@PDA-HA-FA exhibits antitumor efficacy, laying a promising foundation for its potential clinical translation in cancer treatment.