Mesoporous Nanoparticle-Based Ferroptosis and Photothermal Therapy of Cancer

Ferroptosis, a form of cell death, has gained significant attention in tumor therapy, especially for hepatocellular carcinoma (HCC). While sorafenib (SRF) is a potent ferroptosis inducer, single-agent treatments are limited. To address this, we developed a synergistic therapeutic system combining ferroptosis and photothermal therapy. Iron-doped mesoporous poly(levodopa) nanoparticles (Fe-mDOPA) were synthesized and modified with polyethylene glycol (PEG) for coloading SRF and camptothecin (CPT), resulting in Fe-mDOPA@SRF-CPT-PEG. This nanosystem demonstrates high drug-loading efficiency (80%), enhanced biocompatibility, and effective drug delivery. In vitro release studies demonstrated the sustained release of SRF and CPT under tumor-mimicking conditions following laser stimulation. Moreover, Fe-mDOPA@SRF-CPT-PEG exhibited excellent photothermal conversion, promoted glutathione (GSH) depletion, and inhibited GPX4 activity. The combination of photothermal and ferroptosis effects enhanced drug penetration and tumor cell ablation, significantly improving therapeutic efficacy. This multifunctional nanosystem overcomes the limitations of standalone ferroptosis therapy, offering a promising strategy for HCC treatment.