Engineering Research Center of Molecular & Neuroimaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
Angew Chem Int Ed Engl. 2020 Sep 21;59(39):16982-16988. doi: 10.1002/anie.202007474. Epub 2020 Aug 13.
The blood-brain barrier (BBB) restricts access to the brain of more than 98 % of therapeutic agents and is largely responsible for treatment failure of glioblastoma multiforme (GBM). Therefore, it is of great importance to develop a safe and efficient strategy for more effective drug delivery across the BBB into the brain. Inspired by the extraordinary capability of rabies virus (RABV) to enter the central nervous system, we report the development and evaluation of the metal-organic framework-based nanocarrier MILB@LR, which closely mimicked both the bullet-shape structure and surface functions of natural RABV. MILB@LR benefited from a more comprehensive RABV-mimic strategy than mimicking individual features of RABV and exhibited significantly enhanced BBB penetration and brain tumor targeting. MILB@LR also displayed superior inhibition of tumor growth when loaded with oxaliplatin. The results demonstrated that MILB@LR may be valuable for GBM targeting and treatment.
血脑屏障(BBB)限制了超过 98%的治疗药物进入大脑,这在很大程度上导致了多形性胶质母细胞瘤(GBM)的治疗失败。因此,开发一种安全有效的策略,以更有效地将药物透过 BBB 递送至大脑,具有重要意义。受狂犬病病毒(RABV)进入中枢神经系统的非凡能力的启发,我们报告了基于金属有机骨架的纳米载体 MILB@LR 的开发和评估,该载体紧密模拟了天然 RABV 的子弹形状结构和表面功能。MILB@LR 得益于比模仿 RABV 的单个特征更全面的 RABV 模拟策略,表现出显著增强的 BBB 穿透和脑肿瘤靶向能力。当负载奥沙利铂时,MILB@LR 还显示出对肿瘤生长的优异抑制作用。结果表明,MILB@LR 可能对 GBM 的靶向治疗具有重要价值。