Zinc sulfide-based hybrid exosome-coated nanoplatform for targeted treatment of glioblastoma in an orthotopic mouse glioblastoma model

Abstract

Hydroxychloroquine (HCQ) loaded zinc sulfide (ZnS) nanoparticles with hybrid shell were synthesized, characterized and evaluated for the treatment of glioblastoma in vitro and in vivo. These particles, denoted as HCQ@ZnS@eRGD, consist of hollow ZnS nanoparticles loading with the autophagic inhibitor of hydroxychloroquine and covered by a hybrid shell containing exosomes (exo) and iRGD peptide. The hybrid exosomes enable HCQ@ZnS with exceptional permeability across the blood-brain barrier and excellent targeting ability to glioblastoma cells in orthotopic mouse glioblastoma model. ZnS acts as a photosensitizer for reactive oxygen species (ROS) production to inflict damage to organelles in glioblastoma cells. Hydroxychloroquine inhibits autophagic flux, which can subsequently lead to the accumulation of impaired organelles caused by the ROS. As a result, substantial selective damage to glioblastoma was achieved owing to the hybrid exosomes guiding the anti-tumor effects of hydroxychloroquine and ZnS under light illumination. The results provide evidence for the utility of HCQ@ZnS@eRGD as a therapeutic strategy for glioblastoma.