Inflammation-sensing catalase-mimicking nanozymes alleviate acute kidney injury via reversing local oxidative stress

Abstract

Background The reactive oxygen species (ROS) and inflammation, a critical contributor to tissue damage, is well-known to be associated with various disease. The kidney is susceptible to hypoxia and vulnerable to ROS. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of chronic kidney disease and finally, end-stage renal disease. Thus, delivering therapeutic agents to the ROS-rich inflammation site and releasing the therapeutic agents is a feasible solution. Results We developed a longer-circulating, inflammation-sensing, ROS-scavenging versatile nanoplatform by stably loading catalase-mimicking 1-dodecanethiol stabilized Mn3O4 (dMn3O4) nanoparticles inside ROS-sensitive nanomicelles (PTC), resulting in an ROS-sensitive nanozyme (PTC-M). Hydrophobic dMn3O4 nanoparticles were loaded inside PTC micelles to prevent premature release during circulation and act as a therapeutic agent by ROS-responsive release of loaded dMn3O4 once it reached the inflammation site. Conclusions The findings of our study demonstrated the successful attenuation of inflammation and apoptosis in the IRI mice kidneys, suggesting that PTC-M nanozyme could possess promising potential in AKI therapy. This study paves the way for high-performance ROS depletion in treating various inflammation-related diseases. Graphical Abstract

Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin

“…Recently, Choi et al developed nanomicelles able to sense ROS and loaded them with catalase-mimicking 1-dodecanethiol stabilized Mn 3 O 4 . Ultimately, the authors noted that inflammation and apoptosis were attenuated in the renal ischemia/reperfusion injury mouse model [ 170 ].…”

Lipo-MGN Nanoparticle Hypoxia Attenuation Mediated Single-dose Radiotherapy and pH/ROS Responsive T1 Contrast Magnetic Resonance Imaging in Hepatocellular Carcinoma

“…1-Dodecanethiol-stabilized hydrophobic Mn 3 O 4 nanoparticles were prepared as previously described [11].…”

“…MGN has the advantages that it has over other manganese oxide types, such as MnO, MnO 2 and Mn 2 O 3 , for generating more molecular oxygen. Mn 3 O 4 has a higher ROS-scavenging ability owing to the double oxidation states of Mn3 + and Mn2+, which can lead to the conversion of ROS (˙O2-& ˙OH) to molecular oxygen released in in ammation [11,12]. There are a few reports about Mn 3 O 4 nanoparticles (MGNs) for cancer therapy.…”

Biomineralized Nanoscavenger Abrogates Proinflammatory Macrophage Polarization and Induces Neutrophil Clearance through Reverse Migration during Gouty Arthritis

“…Catalasemimicking 1-dodecanethiol stabilized Mn 3 O 4 (dMn 3 O 4 ) NPs entrapped with ROS-sensitive NPs degrade H 2 O 2 as well as suppress TNF-α and IL-6 cytokine secretions, thereby attenuating inflammation in the acute kidney injury mouse model. 47 Previously, we reported a peroxidase-mimicking nanoassembly for anti-inflammation in lipopolysaccharide (LPS)-induced endotoxemia and revealed that the hydrogen peroxide scavenging in LPS-induced macrophages led to reduction in the expression of proinflammatory proteins and cytokines, such as iNOS, Nf-κb, TNFα, and IL-6, thereby preventing aggressive inflammatory responses that cause cognitive damage. 50 Interestingly, our study revealed that reducing intracellular H 2 O 2 levels affected HIF1α, which is considered as the direct activator of the Nf-κb pathway.…”

“…Biocompatible catalytic NPs, such as manganese dioxide (MnO 2 ), − cerium NPs, , and Prussian blue NPs, have the ability to decompose peroxidase and produce oxygen molecules under H 2 O 2 -rich hypoxic environments. Catalase-mimicking 1-dodecanethiol stabilized Mn 3 O 4 (dMn 3 O 4 ) NPs entrapped with ROS-sensitive NPs degrade H 2 O 2 as well as suppress TNF-α and IL-6 cytokine secretions, thereby attenuating inflammation in the acute kidney injury mouse model .…”