Reactive oxygen species-responsive sulfated polysaccharide-based nanogels for ischemic stroke: A precision therapy...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Conventional thrombolytic agents for stroke have limitations including short half-life, poor targeting, and bleeding risks.
• Developing targeted drug delivery systems is crucial for improving therapeutic efficacy and safety in treating thrombotic diseases.

Purpose of the Study:

• To develop a dual-functional nanogel (PGS-SP@UK) for targeted thrombolysis and neuroprotection in ischemic stroke.
• To integrate P-selectin-mediated thrombus targeting with ROS-responsive drug release for enhanced therapeutic outcomes.

Main Methods:

• Synthesized a sulfated polysaccharide-based amphiphilic copolymer capable of encapsulating urokinase (UK).
• Utilized P-selectin targeting and ROS-responsive properties for drug release (H2O2-triggered).
• Evaluated in vitro neuroprotection in OGD/R models and in vivo efficacy in cerebral infarct models, assessing blood-brain barrier penetration and thrombus accumulation.

Main Results:

• The nanogel demonstrated H2O2-triggered UK release (85.79%) with high stability under physiological conditions.
• In vitro studies showed neuroprotective effects via ferroptosis pathway modulation.
• In vivo studies achieved 84.3% recovery in cerebral infarct area through synergistic thrombolysis and oxidative stress mitigation, with efficient BBB penetration and thrombus targeting.

Conclusions:

• The developed dual-functional nanogel (PGS-SP@UK) shows significant potential for clinical application in ischemic stroke treatment.
• This innovative system offers synergistic thrombolysis and neuroprotection, overcoming limitations of conventional therapies.
• The study presents a new therapeutic paradigm for precision medicine in thrombotic disorders.