Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn₃O₄ Nanozymes for Acute Kidney Injury Therapy

Abstract

Reactive oxygen species (ROS) scavenging therapy toward acute kidney injury (AKI) is promising, but no effective ROS scavenging drug has been developed yet. Moreover, cell-free DNA (cfDNA) is also involved in AKI, but the corresponding therapies have not been well developed. To tackle these challenges, Mn 3 O 4 nanoflowers (Nfs) possessing both ROS and cfDNA scavenging activities were developed for better AKI protection as follows. First, Mn 3 O 4 Nfs could protect HK2 cells through cascade ROS scavenging (dismutating • O 2 − into H 2 O 2 by superoxide dismutase-like activity and then decomposing H 2 O 2 by catalase-like activity). Second, Mn 3 O 4 Nfs could efficiently adsorb cfDNA and then decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic efficacy was achieved in both cisplatin-induced and ischemia−reperfusion AKI murine models. Furthermore, Mn 3 O 4 Nfs could be used for the T 1 -MRI real-time imaging of AKI. This study not only offered a promising treatment for AKI but also showed the translational potential of nanozymes.

Nanomedicine in kidney disease

“…Several other substances that were traditionally known to act as antioxidants have been loaded into nanoparticles targeted to RTEC, successfully reducing oxidative stress in the injured kidney and mitigating kidney dysfunction [20 ▪ –26 ▪ ]. A promising strategy has been to co-load within nanocarriers both ROS scavengers along with drugs used to treat other damage mechanisms to further reduce inflammation [27 ▪▪ ] or intracellular calcium, which is believed itself to trigger multiple damage mechanisms [28 ▪▪ ].…”

“…Renal inflammation plays a notorious role in AKI, although systemic treatment with anti-inflammatory medications can present multiple adverse effects that limit their utility. To address this issue, the co-loading of kidney-specific anti-inflammatory agents into nanocarriers together with therapeutics for an additional injury mechanism has been attempted to better mitigate AKI [26 ▪ ,27 ▪▪ ,31 ▪ ,32 ▪ ]. For example, chemokine receptor 4 (CXCR4) is highly expressed in injured RTEC and enhances leukocyte recruitment during AKI.…”

Antioxidant and Prooxidant Nanozymes: From Cellular Redox Regulation to Next‐Generation Therapeutics

“…The nanozyme inhibits O 2 and glucose deprivation‐mediated apoptosis, and endoplasmic reticulum stress, and provides robust neuroprotection against ischemic stroke and reperfusion (I/R) injury of brain tissue (Figure 8). [93] The Mn 3 O 4 nanoflowers with ROS scavenging and cell‐free DNA absorbing properties provide effective protection to the in vivo murine model against cisplatin‐induced and ischemia‐reperfusion acute kidney injury [94] …”

Recent Advances in ROS-Scavenging Metallic Nanozymes for Anti-Inflammatory Diseases: A Review

“… 59 60 61 Thus, MNPs have both drug-carrying and self-therapeutic efficacy for treating various inflammatory diseases ( Table 1 ). 45 59 60 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 In this review, we discuss the roles of recently reported MNPs in the scavenging of reactive oxygen species (ROS) and in anti-inflammatory activities.…”