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 (K 2 S 2 O 8 ) and endogenous hydrogen peroxide (H 2 O 2 ). Sufficient amounts of Fe 3+ and S 2 O 8 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. Fe 3+ was reduced to Fe 2+ by the reducing agents of loaded tannic acid (TA) and intracellular glutathione (GSH), and Fe 2+ was subsequently reacted with S 2 O 8 2- and endogenous H 2 O 2 to produce two types of ROS (˙OH and SO 4 - ˙), showing an excellent anti-tumor effect. This process not only supplied Fe 2+ 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.