Hollow MnO2 nanosystem for glioblastoma sono-immunotherapy based on blood-brain barrier crossing and oxygen supply strategy.

Although smart nanomaterials based on novel therapeutic diagnostics show great potential in cancer treatment, their poor targeting properties and the presence of blood-brain barrier (BBB) in glioblastoma (GBM) significantly reduce the treatment efficacy. This study constructed a multifunctional nanoplatform for magnetic resonance imaging (MRI)-guided sono-immunotherapy of in situ GBM. Hollow manganese dioxide nanoparticles (HMpp NPs) loaded with sonosensitizer Chlorine e6 (Ce6) and surface-modified with transferrin (Tf), named as Ce6@HMpp-Tf NPs. The modification of Tf can help Ce6@HMpp-Tf NPs cross BBB and aggregate at the glioma site, enabling targeted delivery and significantly enhancing the treatment efficiency. Additionally, the carriers can response to acidic tumor microenvironment and be degraded into Mn2+ for MRI monitoring. Furthermore, the therapeutic mechanism was elaborated by inducing the generation of reactive oxygen species (ROS) to exert sonodynamic therapy, activating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway, and activating dendritic cells (DCs) and T cells. Overall, this study demonstrated the significant synergistic anticancer effects of sono-immunotherapy and provided a new method for GBM treatment.