Multifunctional platinum-doped porous FeS2 nanoparticles for photothermal-enhanced photodynamic ferroptosis combination therapy

Explorations on ferroptosis combined with other tumor therapies have attracted much attention in recent years. To enhance the cargo-loaded capacity of the nanoparticles and integrate the ferroptosis as well as apoptosis, here, we reported the Pt-doped porous FeS2 nanoparticles (Pt/pFeS2 NPs) synthesized by the solvothermal method to realize the photothermal-enhanced photodynamic/ferroptosis antitumor combination therapy, with glucose oxidase (GOX)-loaded and 4T1 cell membrane-coated as the multifunctional Pt/pFeS2@GOX@4T1 nanovesicles (NVs). The porous structure provided more sites for Fenton reaction as well as photodynamic effect, which dramatically improve the level of reactive oxygen species. Additionally, the loaded GOX enhanced the generation of endogenous hydrogen peroxide and reduced the pH value of the tumor microenvironment, further promoting the Fenton reaction for ferroptosis. Moreover, Pt catalyzed the degradation of hydrogen peroxide to release oxygen, even facilitating the photodynamic therapy efficacy in the hypoxic tumor microenvironment. The rate of Fenton reaction and photocatalytic reaction were both significantly improved, leading to the acceleration of ferroptosis and photodynamic therapy with the increase of temperature under laser irradiation at 808 nm. Additionally, the in vivo antitumor therapy proved that Pt/pFeS2@GOX@4T1 NVs efficiently accumulated at tumor sites for photoacoustic imaging. To sum up, the multifunctional Pt/pFeS2@GOX@4T1 NVs could achieve photothermal-enhanced photodynamic/ferroptosis combination antitumor therapy and significantly inhibit the growth of 4T1 tumor without side-effects, shedding light on the promising application in photoacoustic image-guided tumor therapy system.