Neisseria meningitidis Opca Protein/MnO2 Hybrid Nanoparticles for Overcoming the Blood–Brain Barrier to Treat Glioblastoma

Abstract The major hurdle in glioblastoma therapy is the low efficacy of drugs crossing the blood–brain barrier (BBB). Neisseria meningitidis is known to specifically enrich in the central nervous system through the guidance of an outer membrane invasion protein named Opca. Here, by loading a chemotherapeutic drug methotrexate (MTX) in hollow manganese dioxide (MnO 2 ) nanoparticles with surface modification of the Opca protein of Neisseria meningitidis , a bionic nanotherapeutic system (MTX@MnO 2 ‐Opca) is demonstrated to effectively overcome the BBB. The presence of the Opca protein enables the drug to cross the BBB and penetrate into tumor tissues. After accumulating in glioblastoma, the nanotherapeutic system catalyzes the decomposition of excess H 2 O 2 in the tumor tissue and thereby generates O 2 , which alleviates tumor hypoxia and enhances the effect of chemotherapy in the treatment of glioblastoma. This bionic nanotherapeutic system may exhibit great potential in the treatment of glioblastoma.