One‐Step Synthesis of Hemin@Au Nanoparticles for Inducing Ferroptosis in Photothermal‐Immunotherapy Against Cancer

ABSTRACT This study presents a one‐step hydrothermal synthesis of Hemin@Au nanoparticles (Hemin@Au NPs), where hemin acts as both reducing and stabilizing agent. Fe 3+ in hemin is reduced to Fe 2+ , transferring electrons to reduce Au 3+ to Au 0 , thereby initiating nanoparticle formation. The resulting NPs show a multifunctional nanoplatform for cancer therapy. The as‐prepared NPs exhibits uniform spherical morphology, high colloidal stability, and efficient near‐infrared photothermal conversion property. Hemin@Au NPs demonstrats pronounced Fenton‐like catalytic activity, facilitating reactive oxygen species generation and ferroptosis induction, supported by elevated intracellular iron levels, enhanced lipid peroxidation, mitochondrial impairment, and downregulation of GPX4 expression in cancer cells. In vitro, Hemin@Au NPs combined with photothermal treatment triggers immunogenic cell death, as indicated by surface exposure of calreticulin, extracellular adenosine triphosphate (ATP) and High Mobility Group Box 1 (HMGB1) release. In vivo evaluation in B16F10 tumor‐bearing mice shows tumor‐specific accumulation of the NPs, significant tumor suppression, and extended survival, with further efficacy enhancement upon combination with CpG oligodeoxynucleotide immunotherapy. The combined regimen promotes dendritic cell maturation, amplifying cytotoxic T‐cell infiltration, and elevating pro‐inflammatory cytokine levels. In summary, Hemin@Au NPs constitute an integrated therapeutic platform that combines ferroptosis, photothermal ablation, and immune activation, with evidence suggesting a potential synergistic interaction between photothermal effects and ferroptosis.