Photothermal Fenton Nanocatalysts for Synergetic Cancer Therapy in the Second Near-Infrared Window

Chemodynamic therapy (CDT) that utilizes endogenous hydrogen peroxide (H 2 O 2 ) to produce reactive oxygen species (ROS) to kill cancer cells has shown a promising strategy for malignant tumor treatment. Nevertheless, limited H 2 O 2 levels in the tumor microenvironment often compromise the therapeutic benefits of CDT, leading to cancer recurrence and metastasis. Herein, a second near-infrared (NIR-II) photothermal Fenton nanocatalyst (PFN) was developed for activatable magnetic resonance imaging (MRI)-guided synergetic photothermal therapy (PTT) and CDT of pancreatic carcinoma. Such a PFN consists of manganese dioxide (MnO 2 ), copper sulfide (CuS), and human serum albumin (HSA), which serve as the activatable imaging contrast agent, the NIR-II photothermal agent and Fenton catalyst, and the stabilizer, respectively. The acidic tumor microenvironment increased the relaxivity of PFN by 2.1-fold, allowing for improved imaging performance and monitoring of nanoparticle accumulation in tumors. Under NIR-II laser irradiation at 1064 nm, PFN generates local heat, which not only permits PTT but also enhances the nanocatalyst-mediated Fenton-like reaction. As such, PFN exerts a synergetic action to completely ablate xenografted tumor models in living animals, while the sole CDT fails to do so. This study thus provides an NIR-II photothermal nanocatalyst for potential treatment of deep-seated tumors.