Simultaneous Blood–Brain Barrier Crossing and Protection for Stroke Treatment Based on Edaravone-Loaded Ceria Nanoparticles
| Autor: | Qunqun Bao, Limin Pan, Yingying Xu, Tiansheng Cheng, Ping Hu, Jianlin Shi, Chenyang Wei |
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| Rok vydání: | 2018 |
| Předmět: |
General Physics and Astronomy
Nanoparticle 02 engineering and technology 010402 general chemistry Blood–brain barrier 01 natural sciences Neuroprotection Rats Sprague-Dawley Cerebral circulation chemistry.chemical_compound Edaravone medicine Animals General Materials Science Stroke chemistry.chemical_classification Drug Carriers Reactive oxygen species General Engineering Cerium Free Radical Scavengers 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences medicine.anatomical_structure chemistry Transcytosis Blood-Brain Barrier Biophysics Nanoparticles Peptides Reactive Oxygen Species 0210 nano-technology |
| Zdroj: | ACS Nano. 12:6794-6805 |
| ISSN: | 1936-086X 1936-0851 |
| DOI: | 10.1021/acsnano.8b01994 |
| Popis: | Cerebral vasculature and neuronal networks will be largely destroyed due to the oxidative damage by overproduced reactive oxygen species (ROS) during a stroke, accompanied by the symptoms of ischemic injury and blood-brain barrier (BBB) disruption. Ceria nanoparticles, acting as an effective and recyclable ROS scavenger, have been shown to be highly effective in neuroprotection. However, the brain access of nanoparticles can only be achieved by targeting the damaged area of BBB, leading to the disrupted BBB being unprotected and to turbulence of the microenvironment in the brain. Nevertheless, the integrity of the BBB will cause very limited accumulation of therapeutic nanoparticles in brain lesions. This dilemma is a great challenge in the development of efficient stroke nanotherapeutics. Herein, we have developed an effective stroke treatment agent based on monodisperse ceria nanoparticles, which are loaded with edaravone and modified with Angiopep-2 and poly(ethylene glycol) on their surface (E-A/P-CeO2). The as-designed E-A/P-CeO2 features highly effective BBB crossing via receptor-mediated transcytosis to access brain tissues and synergistic elimination of ROS by both the loaded edaravone and ceria nanoparticles. As a result, the E-A/P-CeO2 with low toxicity and excellent hemo/histocompatibility can be used to effectively treat strokes due to great intracephalic uptake enhancement and, in the meantime, effectively protect the BBB, holding great potentials in stroke therapy with much mitigated harmful side effects and sequelae. |
| Databáze: | OpenAIRE |
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