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Multiparametric MRI for In Vivo Visualization of Renal Inflammation in Acute Kidney Injury
Chuang Liu1,2, Shuai Wu1, Mingyu Zhang1
1College of Materials Science and Engineering, and College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, People's Republic of China.
Abstract:
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), yet early diagnosis remains challenging owing to the lack of sensitive and specific approaches for in vivo inflammation visualization, which severely limits accurate diagnosis and effective intervention. To address this limitation, this work reports an inflammation-targeting multiparametric MRI strategy based on a nanoprobe (NPs@PEG-PEP) for real-time visualization of AKI-associated inflammatory responses. NPs@PEG-PEP was modified with functional peptides targeting CD137, which is an activation-induced immune receptor serving as an upstream mediator of inflammatory cascades. This approach enables nanoprobes to selectively target and accumulate surrounding inflammatory cells in AKI-affected kidneys. In addition, constructed from NaGdF4 nanoparticles, the nanoprobe simultaneously enhances dynamic contrast-enhanced MRI (DCE-MRI) and susceptibility-weighted imaging (SWI) to capture distinct vascular perfusion differences and inflammatory cell infiltration between injured and contralateral kidneys. The inflammatory imaging signal persists for up to 18 h and correlates well with histopathological findings, including H&E staining and CD11b immunofluorescence. Moreover, the biological safety of the nanoprobe is confirmed via cytotoxicity assays, hemolysis tests, and histopathological evaluations. Overall, this work establishes an inflammation-targeting multiparametric MRI platform that enables spatiotemporal mapping of IRI-induced AKI progression, offering a promising strategy for early diagnosis and therapeutic monitoring.
Insights
This study introduces a novel MRI nanoprobe for visualizing kidney inflammation in acute kidney injury (AKI) caused by renal ischemia-reperfusion injury (IRI). This targeted approach aids in early diagnosis and monitoring of AKI progression.
Area of Science:
- Biomedical imaging
- Nanotechnology
- Renal pathophysiology
Background:
- Renal ischemia-reperfusion injury (IRI) is a primary cause of acute kidney injury (AKI).
- Current diagnostic methods lack sensitivity and specificity for in vivo inflammation visualization, hindering early detection and intervention.
- Targeting inflammatory responses is crucial for understanding and managing AKI.
Purpose of the Study:
- To develop and evaluate an inflammation-targeting multiparametric MRI strategy for real-time visualization of AKI-associated inflammation.
- To assess the efficacy of a novel nanoprobe (NPs@PEG-PEP) in detecting inflammatory cell infiltration in IRI-induced AKI.
- To establish a platform for spatiotemporal mapping of AKI progression.
Main Methods:
- Development of a nanoprobe (NPs@PEG-PEP) functionalized with peptides targeting CD137, an immune activation receptor.
- Utilizing NaGdF4 nanoparticles for simultaneous dynamic contrast-enhanced MRI (DCE-MRI) and susceptibility-weighted imaging (SWI).
- In vivo evaluation of the nanoprobe's targeting ability, imaging signal persistence, and correlation with histopathological findings (H&E, CD11b).
- Assessment of the nanoprobe's biological safety through cytotoxicity assays, hemolysis tests, and histopathology.
Main Results:
- The NPs@PEG-PEP nanoprobe selectively targeted and accumulated in inflammatory cells within AKI-affected kidneys.
- Multiparametric MRI effectively captured differences in vascular perfusion and inflammatory cell infiltration.
- The inflammatory imaging signal demonstrated persistence for up to 18 hours and correlated well with histological evidence of inflammation.
- Biological safety evaluations confirmed the nanoprobe's biocompatibility.
Conclusions:
- An inflammation-targeting, multiparametric MRI platform using a CD137-targeting nanoprobe enables effective visualization of IRI-induced AKI.
- This approach facilitates spatiotemporal mapping of AKI progression, offering a promising strategy for early diagnosis and therapeutic monitoring.
- The developed nanoprobe demonstrates significant potential for improving the management of AKI.
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