Shear force-ROS sequential responsive drug delivery system for improving cerebral thrombosis microcirculation and...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Neuroscience

Background:

• Ischemic stroke poses significant health risks, characterized by cerebral embolism and neurological deficits.
• Effective stroke treatment requires rapid restoration of cerebral blood supply and neurological function.
• Current therapies face challenges in targeted drug delivery to the stroke site.

Purpose of the Study:

• To develop a sequential, targeted drug delivery system for ischemic stroke treatment.
• To address the need for simultaneous thrombolysis and neuroprotection.
• To create a system responsive to the specific microenvironment of cerebral thrombosis and damaged neurons.

Main Methods:

• Construction of a shear force and reactive oxygen species (ROS) dual-responsive system (UK@Fuc/CDPC-PTPCS).
• Sequential delivery of urokinase (UK) for thrombolysis and cytosolic choline (CDPC) for neuroprotection.
• Utilizing fucoidan (Fuc) for platelet targeting and stroke homing peptide (SHp) for neuronal targeting.

Main Results:

• The system successfully targeted cerebral thrombosis sites via Fuc-P-selectin recognition.
• Blood shear force triggered UK release for rapid thrombolysis and restored blood supply.
• SHp-modified core facilitated CDPC release at damaged neurons, mediated by intracellular ROS, providing neuroprotection.

Conclusions:

• The UK@Fuc/CDPC-PTPCS system offers a novel sequential and targeted therapeutic strategy for ischemic stroke.
• This approach effectively addresses both the embolic and functional aspects of stroke pathology.
• The dual-responsive system demonstrates potential for improved clinical outcomes in stroke patients.