Tumor microenvironment activated nanoreactors for chemiluminescence imaging-guided simultaneous elimination of breast tumors and tumor-resident intracellular pathogens

Tumor-resident intracellular pathogens seriously cause tumor metastasis, recurrence, and drug resistance. However, the development of multifunctional platforms for effectively simultaneous elimination of tumors and tumor-resident intracellular pathogens remains challenging. Here, a novel tumor microenvimnment (TME) activated self-reinforcing chemiluminescence (CL) nanosystem with chemiexcited emission, singlet oxygen (O-1(2)), and hydroxyl radicals (center dot OH) generation is reported for simultaneous elimination of tumors and intracellular pathogens in cancer cells. Bis [3,4,6-trichlom-2-(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6) and copper peroxide nanodots (CuO2 NDs) were co-encapsulated by poly (D, L-lactide-co-glycolide) (PLGA) based on oil-in-water (O/W) emulsion method to form chemiluminescence nanocapsules (CPPO/Ce6/CuO2@PLGA) with cascade nanoenzyme activity. Once in cells, the loaded CO2 NDs dissociated under acidic TME, releasing both Cu2+ with glutathione depletion and Fenton catalysis and H2O2 for chemodynamic therapy through a Fenton-like reaction. Meanwhile, the sufficient chemical energy generated by the reaction between H2O2 and CPPO activates Ce6, which enhances chemiluminescence for imaging of tumor sites and further greatly amplifies the generation of O-1(2) for photodynamic therapy. The resulting CPPO/Ce6/CuO2@PLGA showed an excellent therapeutic effect on tumors and intracellular pathogens in vitro and in vivo. This work may offer a facile strategy to prepare multifunctional CL nanoreactors for imaging-guided elimination of both tumors and tumor-resident intracellular pathogens.