Targeted Regulation of Blood–Brain Barrier for Enhanced Therapeutic Efficiency of Hypoxia-Modifier Nanoparticles and Immune Checkpoint Blockade Antibodies for Glioblastoma

• DOI: 10.1021/acsami.1c00347
• Publication Date: 2021-03-08T22:12:29Z
• Authors: Lingtong Meng; Cuirong Wang; Yaping Lu; Gang Sheng; Lin Yang; Zhouyue Wu; Hang Xu; Chao Han; Yingmei Lu; Feng Han
• Keywords: Immune checkpoint; Temozolomide; Tumor Hypoxia; Hypoxia

Glioblastoma is the most destructive type of brain cancer. The blood–brain barrier (BBB) a tremendous obstacle that hinders therapeutic agents, such as chemical drugs and antibodies, from reaching glioblastoma tissues. Meanwhile, abnormal microenvironment extremely restricts expected effects accumulated drugs. Therefore, in present study, BBB-regulating nanovesicles (BRN) are developed to achieve targeted controlled BBB regulation, carrying adenosine 2A receptor (A2AR) agonists perfluorocarbon (PF). red-blood-cell membrane (RBCM) included on outside avoid premature release agents. In presence ultrasonication (US), A2AR released induce both F-actin tight junctions endothelial cells. Subsequently, permeability temporarily increased enables small molecules nanoparticles enter parenchymal high affinity between manganese dioxide temozolomide (TMZ) utilized form multifunctional ameliorate hypoxic microenvironment, which yields improved inhibition combined with radiotherapy. Moreover, aid programmed death ligand-1 (PD-L1) antibody induces tumor-specific immune response. Taken together, findings suggest synergistic combination may have potential amplifying efficacies clinical checkpoint blockade antibodies overcome resistance glioblastoma.