Treatment of Acute Kidney Injury Using a Dual Enzyme Embedded Zeolitic Imidazolate Frameworks Cascade That Catalyzes In Vivo Reactive Oxygen Species Scavenging

Abstract

Significant advances have been made in recent years for the utilization of natural enzymes with antioxidant properties to treat acute kidney injury (AKI). However, these enzymes have been of limited clinical utility because of their limited cellular uptake, poor pharmacokinetic properties, and suboptimal stability. We employed a novel biomimetic mineralization approach to encapsulate catalase (CAT) and superoxide dismutase (SOD) in a zeolitic imidazolate framework-8 (ZIF-8). Next, this SOD@CAT@ZIF-8 complex was anchored with MPEG2000-COOH to yield an MPEG2000-SOD@CAT@ZIF-8 (PSCZ) composite. The composite was then used as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI, remarkably improved intracellular enzyme delivery. This dual-enzyme-embedded metal-organic framework could effectively scavenge reactive oxygen species. In conclusion, the ZIF-8-based “armor plating” represents an effective means of shielding enzymes with improved therapeutic utility to guide the precision medicine-based treatment of AKI.

Debridement of contaminated implants using air-polishing coupled with pH-responsive maximin H5-embedded metal-organic frameworks

“…In detail, with the help of sustained released peptides and metal ions, the cell membranes, the membrane potentials, and the ion homeostasis were initially interrupted, causing obvious membrane dyshomeostasis, membrane permeability, and leakages of the cell component ( Figure 1B ) ( Wen et al, 2021 ; Han et al, 2022 ). Afterwards, ions or peptides passed through the cell membranes to damage the intracellular nucleic acid, hamper the protein formations, block the ATP synthesis and inhibit the enzyme activity ( Figure 1B ) ( Hou et al, 2021 ; Li et al, 2021 ). Additionally, the imidazole ring released from ZIF-8 might exhibit antibacterial effects as well by the disruption of the liposome composed of phospholipid containing the unsaturated fatty acid ( Wan et al, 2021 ).…”

MOF-Based Platform for Kidney Diseases: Advances, Challenges, and Prospects

“…It plays a therapeutic role in AKI. Hou et al used the biomimetic mineralization approach to compress CAT and SOD in ZIF-8 and then fixed with MPEG 2000 -COOH to obtain a more stable and biocompatible MPEG 2000 -SOD@CAT@ZIF-8 (PSCZ) composite [ 138 ]. The transport of intracellular enzymes and the antioxidant effect were greatly enhanced when the composite material was employed as a stabilizing agent with antioxidant qualities for the cascade-based AKI comprehensive treatment.…”

Recent Progress and Prospect of Metal–Organic Framework-Based Nanozymes in Biomedical Application

“…SOD is a crucial enzyme that carries out the simultaneous oxidation and reduction of unstable and toxic ROS, such as 1 O 2 , O 2 • − to H 2 O 2 , and is widely used for the treatment of ROS-induced health problems. However, the in vivo deployment of these enzymes has a few major challenges, including low storage stability, susceptibility to enzymatic aggregation and degradation, poor pharmacokinetics properties, and limited cellular uptake [83,84]. To overcome these challenges, immobilization or encapsulation into the porous matrix has been widely practiced.…”