Molecularly self-assembled nanoplatforms for targeted ROS-scavenging and neuroinflammation alleviation in acute...

Cerebral ischemia-reperfusion injury (CIRI) poses a pivotal barrier to neuronal survival after successful recanalization in acute ischemic stroke. This phenomenon involves multiplexed pathophysiology where oxidative stress-neuroinflammation cascades critically drive neuronal death. Although antioxidative and anti-inflammatory agents hold therapeutic promise, their clinical translation is impeded by insufficient blood-brain barrier (BBB) penetration and the challenge of simultaneously regulating multiple pathological pathways. To address these challenges, we developed a nano therapy integrating traditional Chinese and Western medicine via carrier-free self-assembly of the natural flavonoid baicalein (a Scutellaria baicalensis-derived radical scavenger) and the pharmaceutical rapamycin (an immunosuppressant). This binary nanodrug system achieved high co-loading efficiency via non-covalent interactions. It was further functionalized with DSPE-PEG_2k-Angiopep-2 to enhance colloidal stability, significantly improve BBB penetration, and enhance neuron-targeting capability. The optimized nanoplatform demonstrated potent synergistic neuroprotection through dual-pathway modulation, simultaneously scavenging reactive oxygen species (ROS) and inhibiting inflammation. This approach facilitated targeted drug delivery to ischemic brain lesions, significantly reducing infarct area compared to monotherapies. By effectively integrating traditional Chinese medicine botanicals with Western medicine via molecular nano-engineering, this self-assembled nanoplatform presents a clinically viable strategy for precision intervention in CIRI, successfully bridging Eastern and Western therapeutic paradigms.