Hollow Porous Carbon Coated FeS₂-Based Nanocatalysts for Multimodal Imaging-Guided Photothermal, Starvation, and Triple-Enhanced Chemodynamic Therapy of Cancer

Specific chemical reactions only happen in the tumor region and produce abundant special chemicals to in situ trigger a train of biological and pathological effects that may enable tumor-specific curative effects to treat cancer without causing serious side effects on normal cells or organs. Chemodynamic therapy (CDT) is a rising tactic for cancer therapy, which induces cancer cell death via a localized Fenton reaction. However, the tumor therapeutic effect is limited by the efficiency of the chemical reaction and relies heavily on the catalyst. Here, we constructed hollow porous carbon coated FeS₂ (HPFeS₂@C)-based nanocatalysts for triple-enhanced CDT. Tannic acid was encapsulated in HPFeS₂@C for reducing Fe³⁺ to Fe²⁺, which had a better catalytic activity to accelerate the Fenton reaction. Afterward, glucose oxidase (GOx) in nanocatalysts could consume glucose in the tumor microenvironment and in situ synchronously produce H₂O₂, which could improve Fenton reaction efficiency. Meanwhile, the consumption of glucose could lead to the starvation effect for cancer starvation therapy. The photothermal effects of HPFeS₂@C could generate heat, which further sped up the Fenton process and implemented synergetic photothermal therapy/starvation therapy/CDT. The biodistribution of nanoparticles was investigated by multimodal magnetic resonance, ultrasound, and photoacoustic imaging. These nanocatalysts could trigger the catalytic Fenton reaction at a high degree, which might provide a good paradigm for nanocatalytic tumor therapy.