Self-amplified activatable nanoprodrugs for enhanced chemodynamic/chemo combination therapy

Abstract

Chemodynamic therapy (CDT) has gained increasing attention by virtue of its high tumor specificity and low side effect. However, the low concentration of hydrogen peroxide (H2O2) in the tumor site suppresses the therapeutic efficacy of CDT. To improve the efficacy, introducing other kind of therapeutic modality is a feasible choice. Herein, we develop a self-amplified activatable nanomedicine (PCPTH NP) for chemodynamic/chemo combination therapy. PCPTH NP is composed of a H2O2-activatable amphiphilic prodrug PEG-PCPT and hemin. Upon addition of H2O2, the oxalate linkers within PCPTH NP are cleaved, which makes the simultaneous release of CPT and hemin. The released CPT can not only kill cancer cells but also upregulate the intracellular reactive oxygen species (ROS) level. The elevated ROS level may accelerate the release of drugs and enhance the CDT efficacy. PCPTH NP shows a H2O2 concentration dependent release profile, and can effectively catalyze H2O2 into hydroxyl radical (·OH) under acidic condition. Compared with PCPT NP without hemin, PCPTH NP has better anticancer efficacy both in vitro and in vivo with high biosafety. Thus, our study provides an effective approach to improve the CDT efficacy with high tumor specificity.