Second near-infrared photodynamic therapy and chemotherapy of orthotopic malignant glioblastoma with ultra-small Cu2-xSe nanoparticles

The treatment of malignant glioblastoma is a huge challenge due to the existence of the blood-brain barrier. Herein, we report the treatment of orthotopic malignant glioblastoma with imaging guided second near-infrared (NIR-II) photodynamic therapy and chemotherapy by using drug-loaded ultra-small Cu2-xSe theranostic nanoparticles (NPs). Ultra-small Cu2-xSe NPs possess a strong absorbance in the NIR-II window, and their absorption at 1064 nm is around 2 times that at 808 nm. Their strong NIR-II absorbance and the deeper-tissue penetration of NIR-II light ensure excellent photodynamic therapy performance under irradiation with a 1064 nm laser. We also demonstrate that ultra-small Cu2-xSe NPs can produce vast amounts of reactive oxygen species via electron transfer (for OH generation) and energy transfer (for O-1(2) generation) mechanisms under irradiation. In addition, these NPs can be effectively and locally transported into orthotopic malignant glioblastoma with the assistance of focused ultrasound. The deposited Cu2-xSe NPs can be used for photoacoustic imaging to guide the combined NIR-II photodynamic therapy and chemotherapy. The results show that the tumor growth can be significantly suppressed. This work demonstrates the great potential of drug-loaded ultra-small Cu2-xSe NPs as a promising therapeutic agent for the treatment of orthotopic malignant glioblastoma.