A cerium oxide-based nanomedicine for pH-triggered chemodynamic/chemo combination therapy

Chemodynamic therapy (CDT) is a kind of novel cancer treatment with minimal side effects. As the therapeutic efficacy of a single CDT is usually not satisfactory, combining other therapeutic modalities with CDT is commonly used to improve the therapeutic efficacy. However, such kinds of combination therapeutic systems may suffer from the issue of side effects. Herein, we report a pH-triggered chemodynamic/chemo combination therapeutic nanomedicine based on CeO₂-MnO₂ nanorods (CMNRs). Such a nanomedicine (DOX@PCMNR-RGD) is prepared by coating RGD-conjugated charge-reversal polymers onto the surface of CeO₂-MnO₂ nanoparticles, followed by loading doxorubicin (DOX) onto it. Under mild acidic conditions, the surface charge of nanomedicine may change from negative to positive because of the charge-reversal polymer, making it easy to be internalized into cells. In addition, the tumor overexpressed hydrogen peroxide (H₂O₂) can be selectively catalyzed into highly toxic hydroxyl radicals (˙OH) under acidic conditions by DOX@PCMNR-RGD, showing CDT activity. Meanwhile, the acidic condition can trigger the release of DOX, showing chemotherapeutic activity. Thus, our study provides a pH-triggered chemodynamic/chemo combination therapeutic nanoplatform with minimal side effects.