Pathogenesis-adaptive polydopamine nanosystem for sequential therapy of ischemic stroke.

Area of Science:

• Biomedical Engineering
• Neuroscience
• Materials Science

Background:

• Ischemic stroke is a leading cause of death, with reperfusion therapy often causing secondary brain damage.
• Neuroinflammation following reperfusion presents a dynamic challenge, hindering effective stroke treatment.
• Current stroke therapies lack precision in addressing the evolving inflammatory response.

Purpose of the Study:

• To develop a pathogenesis-adaptive polydopamine nanosystem for sequential and on-demand regulation of post-stroke neuroinflammation.
• To investigate the nanosystem's efficacy in attenuating oxidative stress and reversing pro-inflammatory microglial activation.
• To evaluate the therapeutic potential of this adaptive nanosystem in an in vivo stroke model.

Main Methods:

• Fabrication of a polydopamine nanosystem with intrinsic free radical scavenging properties and a tailored mesostructure.
• Loading of minocycline into the nanosystem for targeted delivery and on-demand release.
• In vivo evaluation of the nanosystem's therapeutic effects on oxidative stress, neuroinflammation, survival rates, and brain recovery in an ischemic stroke model.

Main Results:

• The nanosystem effectively attenuated oxidative stress in the early stage of stroke.
• Minocycline release was triggered by activated matrix metalloproteinase-2, reversing pro-inflammatory microglial states in later stages.
• The sequential therapy strategy demonstrated significantly higher survival rates and improved brain recovery compared to monotherapy and combined therapy.

Conclusions:

• The developed pathogenesis-adaptive polydopamine nanosystem offers a promising sequential and on-demand therapeutic approach for ischemic stroke.
• This strategy effectively regulates post-stroke neuroinflammation, addressing both oxidative stress and microglial activation.
• The nanosystem exhibits satisfactory biosafety, paving the way for advanced ischemic stroke treatments.