Abstract: The complexity of the tumor microenvironment (TME) makes it difficult to completely eliminate tumors with a single treatment. Herein, ion-doped poly(2-nitro-1,4-phenylenediamine) multifunctional nanospheres loaded with indocyanine green (ICG) are constructed for synergistic cancer therapy by photothermal therapy (PTT)/photodynamic therapy (PDT) /chemo-dynamic therapy (CDT). Under 808 nm laser irradiation, ICG as a photosensitizer could generate ¹O₂ and Fe-PNPD acts as a photothermal agent with a photothermal conversion efficiency of 36.65%. Once Fe-PNPD-ICG (FPIs) is internalized into the cancer cells, it triggers the Fenton reaction to produce ·OH, and clears the over-expressed glutathione (GSH) in TME, thereby reducing the antioxidant capacity in the tumor. At the same time, the generated oxygen can reduce hypoxia in TME and enhance the therapeutic effect of PDT. FPIs is an ideal candidate for synergistic PTT/PDT/CDT therapy, and has broad application prospects for tumor therapy.

Key words: Polynitro-1,4-phenylenediamine, Photothermal therapy, Photodynamic therapy, Chemo-dynamic therapy