Reactive oxygen species (ROS)-mediated nanocatalytic
therapy, as conducted by the tumor microenvironment to generate toxic
hydroxyl (
OH) radicals with the assistant of Fenton nanocatalysts, exhibits high
tumor-therapeutic promise due to its high therapeutic selectivity and desirable therapeutic outcome. The mostly explored Fe-based Fenton nanocatalysts-enabled nanocatalytic
cancer therapy substantially suffers from lowed pH condition and the corresponding
therapeutic effect is still far from satisfactory for further clinic application. In this work, we report, for the first time, that
copper (Cu)-based nanocatalysts have the intrinsic capability to catalyze
hydrogen peroxide (H2O2) into
hydroxyl radicals in a wide range pH condition with the comparable and even better performance as compared to mostly explored Fe-based nanocatalysts. Especially, ultrasmall (≤5 nm) PEGylated Cu2-xS nanodots (Cu2-xS-PEG) were fabricated to serve as the novel Fenton nanocatalysts for nanocatalytic
tumor therapy. Importantly, taking the unique advantage of high near infrared (NIR) light absorbance at NIR-II biowindow (1000-1350 nm), light-activated photonic
theranostic modality, i.e. photoacoustic imaging and
photothermal therapy at both NIR-II biowindows was introduced, which could efficiently delineate/monitor the
tumor regions and synergistically enhance Fenton-mediated therapeutic efficacy by photonic
hyperthermia, respectively. Both systematic in vitro and in vivo experiments have demonstrated the high therapeutic efficacy of Cu2-xS-enabled synergistic photothermal
hyperthermia-enhanced nanocatalytic
therapy. This work not only provides a nanoparticle-augmented synergistic
cancer-therapeutic modality, but also enriches the totally new nanocatalyst types for catalytic Fenton reaction-based nanocatalytic
tumor therapy.