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

Abstract

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 Cu_2−xSe theranostic nanoparticles (NPs). Ultra-small Cu_2−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 Cu_2−xSe NPs can produce vast amounts of reactive oxygen species via electron transfer (for ˙OH generation) and energy transfer (for ¹O₂ 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 Cu_2−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 Cu_2−xSe NPs as a promising therapeutic agent for the treatment of orthotopic malignant glioblastoma.