An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuroscience

Background:

• Ischemic stroke presents a significant global health challenge with limited therapeutic options.
• Current treatments suffer from poor specificity, narrow time windows, and reduced efficacy.
• A new approach is needed to improve therapeutic outcomes for ischemic stroke.

Purpose of the Study:

• To design an ischemia-homing bioengineered nano-scavenger for treating ischemic stroke.
• To develop a system capable of targeting specific pathological elements in the ischemic environment.
• To enhance therapeutic efficacy by addressing multiple disease mechanisms simultaneously.

Main Methods:

• Fabrication of a nano-scavenger (TPC@M2 NPs) by loading catalase (CAT) into tannic acid (TA) nanoparticles.
• Camouflaging the nanoparticles with an M2-type microglia membrane.
• Evaluation of the nano-scavenger's ability to chelate iron, scavenge reactive oxygen species (ROS), and cross the blood-brain barrier (BBB).

Main Results:

• TPC@M2 NPs release TA to chelate excess Fe2+ and acid-responsively release CAT to scavenge multiple ROS (·OH, ·O2−, H2O2).
• The M2 microglia membrane facilitates ischemia-homing and BBB crossing.
• The membrane also acts as a therapeutic agent, repolarizing M1 microglia to M2 phenotype.

Conclusions:

• The developed nano-scavenger effectively clears pathogenic elements, reduces inflammation, and protects neurons.
• This approach shows significant promise for treating ischemic stroke.
• The strategy may also be applicable to other inflammation-related diseases.