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Updated: Jul 19, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Modulation of microglial polarization by sequential targeting surface-engineered exosomes improves therapy for
Xintong Liu1, Yunni Hao1, Zhixuan Huang1
1School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People's Republic of China.
Abstract:
Microglia are important cells that act on regulating neuroinflammation and neurofunction after the induction of ischemic stroke (IS). Consequently, the efficient accumulation of drugs within ischemic regions, particularly in microglia, serves as a valuable approach for achieving effective therapy by attenuating microglia-mediated cerebral ischemic injury. In this study, we designed mannose (man)-conjugated luteolin (lut)-loaded platelet-derived exosomes (lut/man-pEXO) as surface engineered multifunctional cascade-delivery drug carriers to target ischemic blood vessels and subsequent microglia to enhance drug accumulation and induce neuroprotection of neurovascular unit (NVU) against IS. The results revealed that as platelets naturally gathered in pathological ischemic cerebral vessels, lut/man-pEXO could bind to platelets and efficiently target ischemic injury sites. Moreover, owing to the selective binding affinity of mannose present in lut/man-pEXO towards the mannose receptor expressed on microglia, lut/man-pEXO exhibited superior microglia-targeting properties, inducing the increased uptake of lut by microglia. As a result, lut/man-pEXO regulated microglia by inhibiting the activation of detrimental M1 and promoting the transition towards the anti-inflammatory type (M2), thus attenuating ischemic damage of NVU by reducing the infarct area, rescuing the damage of blood-brain barrier (BBB) and preventing inflammatory transformation of astrocytes.
Insights
This study developed mannose-conjugated luteolin-loaded platelet-derived exosomes (lut/man-pEXO) to target microglia in ischemic stroke. The engineered exosomes effectively deliver drugs to the brain, reducing inflammation and protecting the neurovascular unit.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Pharmacology
Background:
- Microglia play a crucial role in regulating neuroinflammation and neurofunction following ischemic stroke (IS).
- Targeting microglia in ischemic regions is vital for effective therapy and attenuating cerebral ischemic injury.
- Efficient drug accumulation in microglia is a key challenge in treating IS.
Purpose of the Study:
- To design and evaluate surface-engineered, multifunctional cascade-delivery drug carriers for targeting ischemic stroke.
- To enhance drug accumulation in microglia and induce neuroprotection of the neurovascular unit (NVU).
- To utilize mannose-conjugated luteolin-loaded platelet-derived exosomes (lut/man-pEXO) for targeted delivery.
Main Methods:
- Design of lut/man-pEXO as drug carriers targeting ischemic blood vessels and microglia.
- Evaluation of lut/man-pEXO's ability to bind to platelets and target ischemic injury sites.
- Assessment of mannose receptor-mediated selective binding to microglia and drug uptake.
Main Results:
- lut/man-pEXO demonstrated efficient targeting of ischemic cerebral vessels and injury sites.
- Superior microglia-targeting properties were observed due to mannose-mannose receptor affinity, increasing luteolin uptake.
- lut/man-pEXO modulated microglia from detrimental M1 to anti-inflammatory M2 phenotype, reducing infarct area, protecting the blood-brain barrier (BBB), and preventing astrocyte inflammation.
Conclusions:
- Surface-engineered lut/man-pEXO effectively targets microglia in ischemic stroke.
- This targeted delivery system enhances neuroprotection by modulating microglial activation and reducing ischemic damage.
- lut/man-pEXO represents a promising therapeutic strategy for ischemic stroke treatment.
