Institute of Chemistry, Center for Nanoscience and Nanotechnology , The Hebrew University of Jerusalem , Jerusalem 91904 , Israel.
Institute of Life Science , The Hebrew University of Jerusalem , Jerusalem 91904 , Israel.
ACS Nano. 2018 Aug 28;12(8):7538-7545. doi: 10.1021/acsnano.8b03417. Epub 2018 Jul 10.
Zeolitic Zn-imidazolate cross-linked framework nanoparticles, ZIF-8 NMOFs, are used as "smart" glucose-responsive carriers for the controlled release of drugs. The ZIF-8 NMOFs are loaded with the respective drug and glucose oxidase (GOx), and the GOx-mediated aerobic oxidation of glucose yields gluconic acid and HO. The acidification of the NMOFs' microenvironment leads to the degradation of the nanoparticles and the release of the loaded drugs. In one sense-and-treat system, GOx and insulin are loaded in the NMOFs. In the presence of glucose, the nanoparticles are unlocked, resulting in the release of insulin. The release of insulin is controlled by the concentration of glucose. In the second sense-and-treat system, the NMOFs are loaded with the antivascular endothelial growth factor aptamer (VEGF aptamer) and GOx. In the presence of glucose, the ZIF-8 NMOFs are degraded, leading to the release of the VEGF aptamer, which acts as a potential inhibitor of the angiogenetic regeneration of blood vessels by VEGF. As calcination of the VEGF-generated blood vessels leads to blindness of diabetic patients, the functional NMOFs might act as "smart" materials for the treatment of macular diseases. The potential cytotoxicity of the NMOFs originated from the GOx-generated HO is resolved by the co-immobilization of the HO-scavanger catalase in the NMOFs.
沸石咪唑酯骨架纳米颗粒（ZIF-8 NMOFs）被用作“智能”葡萄糖响应型药物载体，用于控制药物的释放。ZIF-8 NMOFs 负载相应的药物和葡萄糖氧化酶（GOx），GOx 介导的葡萄糖有氧氧化生成葡萄糖酸和 HO。NMOFs 微环境的酸化导致纳米颗粒降解和负载药物的释放。在一种感测-治疗系统中，GOx 和胰岛素被装载在 NMOFs 中。在葡萄糖存在的情况下，纳米颗粒被解锁，导致胰岛素的释放。胰岛素的释放受葡萄糖浓度的控制。在第二种感测-治疗系统中，NMOFs 装载了抗血管内皮生长因子适体（VEGF 适体）和 GOx。在葡萄糖存在的情况下，ZIF-8 NMOFs 被降解，导致 VEGF 适体的释放，VEGF 适体作为 VEGF 诱导的血管生成再生的潜在抑制剂。由于 VEGF 生成的血管的钙化导致糖尿病患者失明，因此功能化的 NMOFs 可以作为治疗黄斑疾病的“智能”材料。NMOFs 中产生的 HO 引起的潜在细胞毒性通过在 NMOFs 中共同固定 HO 清除剂过氧化氢酶得到解决。
