Shell-Sheddable Polymeric Micelles Alleviate Oxidative Stress and Inflammation for Enhanced Ischemic Stroke Therapy.
Zhenhua WangJingmei PanRuiting YuanMo ChenXing GuoShaobing ZhouPublished in: Nano letters (2023)
As a ROS scavenger, resveratrol exerts a neuroprotective effect by polarizing the M1 microglia to the anti-inflammatory M2 phenotype for ischemic stroke treatment. However, the obstruction of the blood-brain barrier (BBB) seriously impairs the efficacy of resveratrol. Herein, we develop a stepwise targeting nanoplatform for enhanced ischemic stroke therapy, which is fabricated by pH-responsive poly(ethylene glycol)-acetal-polycaprolactone-poly(ethylene glycol) (PEG-Acetal-PCL-PEG) and modified with cRGD and triphenylphosphine (TPP) on a long PEG chain and a short PEG chain, respectively. The as-designed micelle system features effective BBB penetration through cRGD-mediated transcytosis. Once entering the ischemic brain tissues and endocytosed by microglia, the long PEG shell can be detached from the micelles in the acidic lysosomes, subsequently exposing TPP to target mitochondria. Thus, the micelles can effectively alleviate oxidative stress and inflammation by enhanced delivery of resveratrol to microglia mitochondria, reversing the microglia phenotype through the scavenging of ROS. This work offers a promising strategy to treat ischemia-reperfusion injury.
Keyphrases
- drug delivery
- oxidative stress
- cancer therapy
- ischemia reperfusion injury
- drug release
- dna damage
- inflammatory response
- blood brain barrier
- cell death
- reactive oxygen species
- neuropathic pain
- atrial fibrillation
- diabetic rats
- induced apoptosis
- cerebral ischemia
- anti inflammatory
- white matter
- multiple sclerosis
- resting state
- replacement therapy
- heat shock
- subarachnoid hemorrhage