Macrophage biomimetic intelligent hollow MnO2 nanoparticle for synergistic sonodynamic-immunotherapy of glioblastoma by crossing blood brain barrier

Abstract

Though emerging novel theranostics based intelligent nanomaterials for cancers are promising ways to solve the disadvantages of traditional therapeutic methods, poor targeting of these nanomaterials and the presence of blood–brain barrier (BBB) in glioblastoma (GBM) seriously reduces the efficacy of GBM treatment. Herein, an intelligent nanoparticle consisting of macrophage membrane coated hollow manganese dioxide loading ce6 (MM-HMnO2@Ce6) was prepared, which could be used for magnetic resonance imaging (MRI) guided sonodynamic therapy (SDT)-immunotherapy of in situ GBM. Comparing to early reports, MM-HMnO2@Ce6 could target intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) receptors on endothelial cells of GBM, and cross BBB, which enhanced the efficiency of GBM treatment. What’s more, the as-prepared nanoparticle also monitored the process of targeting and crossing BBB by MRI due to its tumour microenvironment (TME) responsive feature. What’s more, the detailed therapeutic mechanisms were also determined to be by generating reactive oxygen species (ROS), activating immature DCs and activating the cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway. Overall, this work showcases a remarkable synergistic anticancer effect of SDT-immunotherapy, and also proposes new avenues for research in utilizing MnO2 nanomaterials for GBM treatment.

Keywords

• Blood–brain barrier
• Sonodynamic therapy
• Immunotherapy
• Therapeutic mechanism
• Magnetic resonance imaging