Glucose-Responsive Metal–Organic-Framework Nanoparticles Act as “Smart” Sense-and-Treat Carriers

Abstract

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.

Multi‐enzyme Cascade Reactions in Metal‐organic Frameworks

“…[76][77][78] By further encapsulation of catalase, a H 2 O 2scavanger, within ZIF-8, the potential cytotoxicity of the GOx-generated H 2 O 2 could be eliminated due to the consumption of H 2 O 2 catalyzed by catalases. [54] Therefore, the cascade reaction of GOx/catalases within MOF enabled a smart glucose-responsive carrier without significant cytotoxicity. More recently, Zhang and co-workers reported that by surface coating enzyme@MOF with natural cell membrane, the versatile biomimetic nanoplatforms could realize specific cellular uptake and the preferential tumor accumulation, due to the surface receptors on the membrane endowed enzyme@-MOF with the capacity to bypass the biological barriers, resulting in an effective drug or enzyme delivery.…”

“…Furthermore, due to the high enzyme loading capacity, biodegradability, and high biocompatibility in vitro and in vivo, multi-enzyme@MOF systems have also shown considerable promise in catalytic nanomedicine applications, such as glucose oxidase (GOx) and horseradish peroxidase (HRP) or chloroperoxidase (CPO) co-encapsulated in MOFs induced high toxic reactive oxygen species (ROS) generation for tumor cell therapy, [44,45] and GOx and catalase co-immobilized within MOFs enabled smart drug delivery with negligible cytotoxicity. [54] In addition, with extraordinary chemical robustness and high enzyme encapsulation capacity of MOFs, the multi-enzyme@MOF systems allow new possibilities in artificial and hybrid cells design, enabling new potentials in cell manipulation and enzyme replacement therapy. [47,57] Although a series of review articles on the diversity of enzymatic cascades [1,[58][59][60][61][62] and their immobilization in macromolecular scaffolds have been published within the past few years, [9,18,21,22,31,[63][64][65][66][67][68][69] none has particularly focused on the immobilization strategies of multi-enzyme within MOFs and their cutting-edge applications.…”

Degradation of ZIF-8 in phosphate buffered saline media

“…doxorubicin and insulin) for treatment of diseases ranging from cancer to diabetes. 22,23 The use of ZIF-8 was extended to bio-catalytic application with ZIF particles encapsulating and protecting enzymes such as horseradish peroxidase (HRP), catalase, lipase from inhospitable environments. 9 Then, protective properties of ZIF-8 were tested for the bio-preservation of viruses and yeast cells showing that the ZIF-8 coatings can be controllably assembled and dissolved.…”

Fast Immobilization of Human Carbonic Anhydrase II on Ni-Based Metal-Organic Framework Nanorods with High Catalytic Performance

“…Metal-organic frameworks (MOFs) are a new kind of organic-inorganic hybrid porous material [23,24]. Since MOF materials are considered to be potent supporting matrices for enzyme immobilization, many kinds of commodity enzymes were immobilized successfully [25][26][27][28]. However, other researchers have spent their energy on the design of Zn 2+ , Cu 2+ or Fe 3+ -based MOFs for enzyme immobilization [29][30][31].…”