ROS-responsive quercetin-based polydopamine nanoparticles for targeting ischemic stroke by attenuating oxidative...

Area of Science:

• Nanomedicine
• Neuroscience
• Pharmacology

Background:

• Ischemic stroke (IS) presents significant morbidity and disability challenges.
• Current IS therapies face limitations including poor blood-brain barrier (BBB) penetration and side effects.
• Developing multi-target neuroprotective agents with improved BBB permeability is crucial for IS treatment.

Purpose of the Study:

• To develop a novel nanotherapeutic strategy for ischemic stroke (IS) using quercetin (Que) and polydopamine (PDA).
• To enhance BBB penetration and therapeutic efficacy of quercetin through nanotechnology.
• To evaluate the neuroprotective effects of the developed nanoparticles in vitro and in vivo.

Main Methods:

• Quercetin (Que) was encapsulated within polydopamine (PDA) nanoparticles (NPs) via oxidative self-assembly.
• Rabies virus glycoprotein (RVG29) was surface-functionalized onto the NPs to enhance cellular uptake.
• ROS-responsive degradation properties and cellular internalization were assessed in SH-SY5Y cells.
• In vivo efficacy was evaluated in a rat model of middle cerebral artery occlusion (MCAO).

Main Results:

• Que@DAR NPs demonstrated improved dispersion stability and ROS-responsive degradation.
• RVG29 significantly enhanced cellular uptake of Que@DAR NPs in neuroblastoma cells.
• Que@DAR NPs reduced oxidative damage, promoted M2 microglia polarization, inhibited neuroinflammation, and decreased neuronal apoptosis.
• Neurological dysfunction was significantly ameliorated in MCAO rats treated with Que@DAR NPs.

Conclusions:

• Que@DAR NPs represent a safe and effective strategy for precision treatment of ischemic stroke.
• The developed nanocarrier system overcomes limitations of traditional IS therapies.
• This approach holds significant potential for advancing IS therapeutic interventions.