Journal
ACS NANO
Volume 12, Issue 7, Pages 6794-6805Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b01994
Keywords
stroke; blood-brain barrier; ceria nanoparticles; edaravone; reactive oxygen species
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Funding
- National Natural Science Foundation of China [51502326, 51702349]
- Shanghai Yangfan Program [16YF1412800]
- Youth Innovation Promotion Association Chinese Academy of Sciences [2017299]
- Science Foundation for Youth Scholar of State Key Laboratory of High Performance Ceramics and Superfine Microstructures [SKL201704]
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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
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