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Microglial Membranes Wrapped Ultrasmall Medium-Entropy Ru Single-Atom Nanozyme: Enhanced Catalysis for Accelerating
Jiebo Li1,2,3,4, Penghui Wei1,2,3,4, Yuanbo Pan5
1Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Abstract:
Intracerebral hemorrhage (ICH) causes severe secondary brain injury (SBI) via excessive inflammation and reactive oxygen species (ROS), and current treatments lack effective dual-target efficacy. In this study, we designed a microglial membrane-wrapped single-atom nanozyme (PtRhIr/Ru SAN@M) by anchoring a single atom of Ru onto ultrasmall, medium-entropy PtRhIr alloys. This design integrates two underutilized strategies, single-atom nanozymes (SANs) and medium-entropy catalysts, to address critical therapeutic gaps in ICH therapy. PtRhIr/Ru SAN@M exhibited enhanced catalytic activity with superior Hydroxyl radical (•OH) scavenging and superoxide dismutase (SOD)-like and catalase (CAT)-like performances compared to Ru-free PtRhIr@M, enabled by electronically modulated active sites. Fluorescence imaging confirmed its ability to penetrate the blood-brain barrier (BBB) and accumulate in post-ICH neuroinflammatory regions. Both in vitro and in vivo experiments demonstrated that PtRhIr/Ru SAN@M repolarized microglia from the M1 to the M2 phenotype, disrupting the neuroinflammatory cycle and halting neuronal death. Therapeutic intervention with PtRhIr/Ru SAN@M significantly increased survival rates, restored neurological function, and enhanced spatial memory after ICH. This study pioneers the integration of SANs with medium-entropy alloys for ICH, offering a dual-target ROS-inflammation regulatory strategy and a generalizable platform for ROS-related degenerative disease therapies.
Insights
This study introduces a novel nanozyme therapy for intracerebral hemorrhage (ICH) that effectively reduces inflammation and oxidative stress. The treatment improved survival rates and neurological function in ICH models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Neuroscience
Background:
- Intracerebral hemorrhage (ICH) causes secondary brain injury (SBI) through inflammation and reactive oxygen species (ROS).
- Existing treatments for ICH lack effective dual-target efficacy against inflammation and ROS.
- There is a critical need for innovative therapeutic strategies to mitigate ICH-induced brain damage.
Purpose of the Study:
- To design and evaluate a novel microglial membrane-wrapped single-atom nanozyme (PtRhIr/Ru SAN@M) for treating ICH.
- To investigate the dual-target efficacy of the nanozyme in scavenging ROS and modulating neuroinflammation.
- To assess the therapeutic potential of PtRhIr/Ru SAN@M in preclinical ICH models.
Main Methods:
- Synthesized ultrasmall, medium-entropy PtRhIr alloys and anchored single-atom Ruthenium (Ru) to create PtRhIr/Ru SAN@M.
- Wrapped the nanozyme with microglial membranes to enhance blood-brain barrier (BBB) penetration.
- Evaluated catalytic activities (SOD, CAT, •OH scavenging) and neuroprotective effects in vitro and in vivo models of ICH.
Main Results:
- PtRhIr/Ru SAN@M demonstrated superior ROS scavenging and enzyme-like activities compared to controls.
- The nanozyme successfully penetrated the BBB and accumulated in brain regions affected by ICH.
- Treatment with PtRhIr/Ru SAN@M repolarized microglia from M1 to M2 phenotype, reduced neuronal death, and improved neurological function and survival rates.
Conclusions:
- The developed PtRhIr/Ru SAN@M offers a promising dual-target therapeutic strategy for ICH by regulating ROS and inflammation.
- This study presents a generalizable platform for using single-atom nanozymes and medium-entropy alloys in treating ROS-related diseases.
- The findings highlight the potential of advanced nanomaterials in addressing critical unmet needs in neurotrauma therapy.
