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Inhalable Ce Nanozyme-Backpacked Phage Aims at Ischemic Cerebral Injury by M1-Microglia Hitchhiking
Zhixin Zhu1, Lulu Jin1, Qiaoxuan Wang1
1MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China.
Advanced Materials (Deerfield Beach, Fla.)
|April 15, 2025
Summary
This study introduces a novel inhalable nanomedicine using M13 bacteriophages loaded with cerium zirconium oxide nanoparticles (CZM). CZM targets M1-polarized microglia, effectively delivering antioxidants to treat ischemic stroke and reduce neuroinflammation.
Area of Science:
- Nanomedicine
- Neuroscience
- Biotechnology
Background:
- Ischemic stroke causes significant brain injury due to oxidative stress and inflammation.
- Traditional antioxidants have poor delivery efficiency and off-target toxicity, limiting their effectiveness in the brain.
- M13 bacteriophages can be specifically targeted to M1-polarized microglia, which are involved in neuroinflammation.
Purpose of the Study:
- To develop an inhalable nanomedicine for targeted delivery of antioxidants to treat ischemic cerebral injury.
- To investigate the uptake of M13 bacteriophages by different microglia phenotypes.
- To evaluate the efficacy of the developed nanomedicine in alleviating oxidative damage and neuronal apoptosis.
Main Methods:
- Development of a bio-active, inhalable cerium zirconium oxide-backpacked-M13 phage (CZM) nanomedicine.
- Demonstration of M13 bacteriophage uptake by different microglia phenotypes.
- Assessment of CZM delivery to ischemic brain regions (core and penumbra).
- Evaluation of CZM's ability to eliminate reactive oxygen species (ROS) and reduce neuronal apoptosis.
Main Results:
- CZM is extensively and specifically delivered to the ischemic core and penumbra via M1 microglia migration.
- CZM effectively eliminates ROS generated by hyperactive M1-polarized microglia.
- Non-invasive administration of CZM alleviates oxidative damage and apoptosis of neurons.
Conclusions:
- CZM represents a secure and effective strategy for targeted therapy of ischemic cerebral injury.
- This inhalable nanomedicine shows promise for treating neuroinflammatory diseases.
- Targeting M1 microglia with M13 bacteriophages offers a novel approach for nanomedicine delivery in the brain.
