Light-Induced Caspase-3-Responsive Chimeric Peptide for Effective PDT/Chemo Combination Therapy with Good Compatibility.

Abstract

Activated doxorubicin (DOX) often has severe systemic toxicity and side effects due to its inability to distinguish tumor cells from normal cells, which seriously affects the prognosis of patients. Here, we synthesized an inactivated a DOX prodrug that could be selectively activated by a light-induced caspase-3 enzyme in the tumor site. In the absence of light, this uniformly dispersed nanoparticle avoided the unnecessary toxicity under physiological conditions. Upon the laser irradiating to the tumor area of interest, the nanoparticles can produce a large amount of reactive oxygen species (ROS) to induce cell apoptosis and activate caspase-3 enzyme to release DOX selectively. Meanwhile, the produced ROS can also combine with activated DOX to cause more potent tumor damage. The experiments demonstrated that the light can effectively activate DOX drug through a series of cascade events and the subsequent synergistic therapy both in vitro and in vivo. This strategy achieved excellent therapeutic outcomes and minimal adverse effects, which should significantly improve the dilemma of traditional chemotherapy.