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- W2885668194 abstract "Current treatments for ischemic stroke are insufficient. The lack of effective pharmacological approaches can be mainly attributed to the difficulty in overcoming the blood–brain barrier. Here, we report a simple strategy to synthesize protease-responsive, brain-targeting nanoparticles for the improved treatment of stroke. The resulting nanoparticles respond to proteases enriched in the ischemic microenvironment, including thrombin or matrix metalloproteinase-9, by shrinking or expanding their size. Targeted delivery was achieved using surface conjugation of ligands that bind to proteins that were identified to enrich in the ischemic brain using protein arrays. By screening a variety of formulations, we found that AMD3100-conjugated, size-shrinkable nanoparticles (ASNPs) exhibited the greatest delivery efficiency. The brain targeting effect is mainly mediated by AMD3100, which interacts with CXCR4 that is enriched in the ischemic brain tissue. We showed that ASNPs significantly enhanced the efficacy of glyburide, a promising stroke therapeutic drug whose efficacy is limited by its toxicity. Due to their high efficiency in penetrating the ischemic brain and low toxicity, we anticipate that ASNPs have the potential to be translated into clinical applications for the improved treatment of stroke patients." @default.
- W2885668194 created "2018-08-22" @default.
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- W2885668194 date "2018-08-14" @default.
- W2885668194 modified "2023-10-18" @default.
- W2885668194 title "Thrombin-Responsive, Brain-Targeting Nanoparticles for Improved Stroke Therapy" @default.
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- W2885668194 doi "https://doi.org/10.1021/acsnano.8b04787" @default.
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