Enhanced catalytic activity of Fe 3 O 4 -carbon dots complex in the Fenton reaction for enhanced immunotherapeutic and oxygenation effects.

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3 O4 -carbon dots complex (Fe3 O4 -CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3 O4 -CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3 O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3 O4 -CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3 O4 -CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3 O4 -CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3 O4 -CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3 O4 -CDs@Fc is a promising immune-antitumor drug.