Related Experiment Video
Updated: Mar 20, 2026
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
A Rsv@HMnO2-HA nanozyme for AKI therapy via targeting inflammatory storm and activating SIRT1/PGC-1α to restore
Jiaxin Su1, Lingcheng Wu2, Huiru Zhu3
1Department of Radiology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing 400014, PR China; Clinical Pathology Laboratory of Pathology Diagnostic Center, and Molecular Medicine Diagnostic & Testing Center, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong Distinct, Chongqing 400016, PR China.
Introduction:
Acute kidney injury (AKI) is a devastating global health burden. Its pathogenesis, particularly in ischemia/reperfusion (I/R) injury, centers on a vicious cycle between a reactive oxygen species (ROS)-driven inflammatory storm and severe mitochondrial dysfunction in renal tubular cells. While activation of the SIRT1/PGC-1α pathway is a promising therapeutic target for mitochondrial recovery, its potent agonist resveratrol (Rsv) suffers from poor bioavailability, and monotherapy fails to address the concomitant inflammatory pathology.
Objective:
This study aimed to develop a kidney-targeted theranostic nanoplatform that synergistically breaks this pathological cycle. We hypothesized that a nanoplatform co-delivering Rsv and a ROS-scavenging component could concurrently suppress inflammation via direct ROS elimination and restore mitochondrial homeostasis via SIRT1/PGC-1α activation, with integrated magnetic resonance imaging (MRI) capability for monitoring.
Methods:
We engineered a theranostic nanoplatform designated Rsv@HMnO2-HA (HMRH NPs). The platform was constructed by loading Rsv into hollow mesoporous manganese dioxide (HMnO2) nanozymes, followed by surface coating with hyaluronic acid (HA) for active targeting to CD44 receptors over expressed on injured renal tubules. The system's physicochemical properties were thoroughly characterized. Its therapeutic efficacy and theranostic performance were systematically evaluated in a well-established murine model of renal I/R-induced AKI, using a combination of biochemical assays, histological analysis, molecular biology techniques, and in vivo MRI.
Results:
HMRH NPs successfully accumulated in injured kidneys and disassembled in situ. The HMnO2 shell effectively scavenged excess ROS, attenuating the inflammatory response. The co-released Rsv activated the SIRT1/PGC-1α pathway, restored mitochondrial biogenesis, and improved cellular energy homeostasis. The released Mn2+ ions enabled clear T1-weighted MRI contrast, allowing real-time visualization of renal targeting and therapeutic progression.
Conclusion:
The results conclusively demonstrate that the HMRH NPs successfully implements a synergistic two-pronged therapeutic strategy. By co-delivering a ROS-scavenger and a mitochondrial-regenerative agent directly to the site of injury, the platform effectively disrupts the critical pathological crosstalk between inflammation and mitochondrial damage in AKI. This work presents a holistic, targeted, and image-guided nanomedicine strategy, offering a promising approach for the effective treatment and monitoring of AKI.
