Selenium‐Doped Carbon Quantum Dots Act as Broad‐Spectrum Antioxidants for Acute Kidney Injury Management

Abstract

The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium‐doped carbon quantum dots (SeCQDs) have broad‐spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS‐related diseases.

Reactive Oxygen Species (ROS)-Responsive Nanomedicine for Solving Ischemia-Reperfusion Injury

“…(E) The time-dependent bio-distribution of 89 Zr-DFO-SeCQDs in healthy ICR mice via MIP-PET images; The CRE (F) and BUN (G) concentration in serum among groups after various treatments (** P < 0.01, **** P < 0.0001, NS: no significant difference). Reproduced with permission from Rosenkrans et al ( 2020 ). Copyright 2020, Wiley.…”

“…In comparison, Cai's lab successfully developed two nanomedicines specifically targeting to the kidney. Both nanoparticles, SeCQDs and DONs (DNA origami nanostructures) predominantly accumulated in the health murine kidney with ~10 and ~27%ID/g, respectively, while the kidney after AKI further enhanced the accumulation of nanoparticles ( Figure 1E ) (Jiang et al, 2018 ; Rosenkrans et al, 2020 ). With oxidant-sensitive structures (e.g., doped selenium and nuclei acid), SeCQDs and DONs efficiently removed excessive ROS from renal cells ( Figures 1F,G ).…”

<p>Selenium-Doped Carbon Quantum Dots Efficiently Ameliorate Secondary Spinal Cord Injury via Scavenging Reactive Oxygen Species</p>

“…As shown in Figure 3B and Figure S8B , the cell viability of astrocytes and N2a cells increased with the increase in Se-CQDs, indicating that Se-CQDs could significantly reduce H 2 O 2 -induced cell death, which is consistent with the previous report. 39 Moreover, the intracellular ROS levels with or without treatment with Se-CQDs were investigated, and the results are shown in Figure 3C and 3D . After treatment with Se-CQDs, the fluorescence intensity of DCF was significantly reduced, indicating the effective reduction of ROS levels by Se-CQDs.…”

“…The protection effect should be ascribed to the excellent ROS-scavenging ability of Se-CQDs. 39 , 55 As a result, these Se-CQDs reduced the inflammation, astrogliosis, and apoptosis induced by secondary injury, which ultimately led to effective restoration of locomotor function in TSCI rats. In general, our findings suggest that Se-CQDs may serve as a promising therapeutic strategy for TSCI treatment by attenuating the exacerbation of the secondary injury cascade after TSCI.…”

“…[46][47][48][49] The formation of glial scars can interrupt neural pathways of the spinal cord and suppress the recovery of locomotor function. 39,[49][50][51][52] Therefore, we evaluated the formation of glial scars by the co-immunostaining of CS56 and GFAP (indicating the activated astrocytes 53,54 ) at 8 weeks after the operation. As compared with the saline-treated group, the Se-CQDstreated groups showed a significant reduction in CS56 and GFAP expression ( Figure 6B), indicating that the scavenging of ROS by Se-CQDs could effectively reduce the activation of astrocytes and the formation of glial scars.…”