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Glucose-Responsive Metal-Organic-Framework Nanoparticles Act as "Smart" Sense-and-Treat Carriers.

ACS nano (2018-07-04)
Wei-Hai Chen, Guo-Feng Luo, Margarita Vázquez-González, Rémi Cazelles, Yang Sung Sohn, Rachel Nechushtai, Yossi Mandel, Itamar Willner
ABSTRACT

Zeolitic Zn2+-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 H2O2. 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 H2O2 is resolved by the co-immobilization of the H2O2-scavanger catalase in the NMOFs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
8-Hydroxypyrene-1,3,6-trisulfonic acid trisodium salt, ≥96%
Sigma-Aldrich
7-Hydroxycoumarin-3-carboxylic acid, suitable for fluorescence, ≥98.0% (TLC)