Fe-based cyclically catalyzing double free radical nanogenerator for tumor-targeted chemodynamic therapy

The prosperity of chemodynamic therapy provides a new strategy for tumor treatment. However, the lack of reactive oxygen species and the specific reductive tumor microenvironment have limited the further development of chemodynamic therapy. Herein, we reported a Fe-based cyclically catalyzing double free radical system for tumor therapy by catalyzing exogenous potassium persulfate (K₂S₂O₈) and endogenous hydrogen peroxide (H₂O₂). Sufficient amounts of Fe³⁺ and S₂O₈^2- were delivered to tumor sites via tumor-targeted hyaluronic acid (HA) encapsulated mesoporous silica nanoparticles (MSNs) and released under the dual stimulation of acid and hyaluronidase (HAase) in the tumor microenvironment. Fe³⁺ was reduced to Fe²⁺ by the reducing agents of loaded tannic acid (TA) and intracellular glutathione (GSH), and Fe²⁺ was subsequently reacted with S₂O₈^2- and endogenous H₂O₂ to produce two types of ROS (˙OH and SO₄^-˙), showing an excellent anti-tumor effect. This process not only supplied Fe²⁺ for the catalysis of active substances, but also reduced the concentration of reduced substances in cells, which was conducive to the existence of free radicals for the efficient killing of tumor cells. Therefore, this iron-based catalysis of exogenous and exogenous active substances to realize a dual-radical oncotherapy nanosystem would provide a new perspective for chemodynamic therapy.