Targeted Regulation of Blood–Brain Barrier for Enhanced Therapeutic Efficiency of Hypoxia-Modifier Nanoparticles and Immune Checkpoint Blockade Antibodies for Glioblastoma
| العنوان: | Targeted Regulation of Blood–Brain Barrier for Enhanced Therapeutic Efficiency of Hypoxia-Modifier Nanoparticles and Immune Checkpoint Blockade Antibodies for Glioblastoma |
|---|---|
| المؤلفون: | Lin Yang, Hang Xu, Gang Sheng, Zhouyue Wu, Feng Han, Cuirong Wang, Lingtong Meng, Ying-Mei Lu, Chao Han, Ya-Ping Lu |
| المصدر: | ACS Applied Materials & Interfaces. 13:11657-11671 |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Materials science, medicine.medical_treatment, Blood–brain barrier, Targeted therapy, Mice, 03 medical and health sciences, Drug Delivery Systems, 0302 clinical medicine, Immune system, Purinergic P1 Receptor Agonists, medicine, Animals, Humans, General Materials Science, Receptor, Immune Checkpoint Inhibitors, Mice, Inbred BALB C, Temozolomide, Tight junction, Brain Neoplasms, Immune checkpoint, Blockade, 030104 developmental biology, medicine.anatomical_structure, Blood-Brain Barrier, 030220 oncology & carcinogenesis, Cancer research, Nanoparticles, Tumor Hypoxia, Glioblastoma, medicine.drug |
| الوصف: | Glioblastoma is the most destructive type of brain cancer. The blood-brain barrier (BBB) is a tremendous obstacle that hinders therapeutic agents, such as chemical drugs and antibodies, from reaching glioblastoma tissues. Meanwhile, the abnormal microenvironment of glioblastoma extremely restricts the expected therapeutic effects of accumulated drugs. Therefore, in the present study, BBB-regulating nanovesicles (BRN) are developed to achieve targeted and controlled BBB regulation, carrying adenosine 2A receptor (A2AR) agonists and perfluorocarbon (PF). The red-blood-cell membrane (RBCM) is included on the outside to avoid the premature release of therapeutic agents. In the presence of ultrasonication (US), A2AR agonists are released and induce effects on both F-actin and tight junctions of endothelial cells. Subsequently, BBB permeability is temporarily increased and enables small molecules and nanoparticles to enter brain parenchymal tissues. The high affinity between manganese dioxide and temozolomide (TMZ) is utilized to form multifunctional nanoparticles to ameliorate the hypoxic microenvironment, which yields improved glioblastoma inhibition combined with radiotherapy. Moreover, with the aid of targeted BBB regulation, programmed death ligand-1 (PD-L1) antibody induces a tumor-specific immune response. Taken together, the findings suggest that synergistic combination may have the potential in amplifying the therapeutic efficacies of clinical drugs and immune checkpoint blockade antibodies to overcome the therapeutic resistance of glioblastoma. |
| تدمد: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.1c00347 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fe526adf7028e198b4017d4d88f39c2 https://doi.org/10.1021/acsami.1c00347 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....3fe526adf7028e198b4017d4d88f39c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19448252 19448244 |
|---|---|
| DOI: | 10.1021/acsami.1c00347 |