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.

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A highly dispersed CuO catalyst was prepared by the deposition-precipitation method and evaluated for the catalytic epoxidation of styrene with tert-butyl hydroperoxide (TBHP) as the oxidant under solvent acetonitrile conditions. Compared with MgAl hydrotalcite (MgAl-HT)-, MgO-, TiO-, C-, and MCM-22-supported catalysts, CuO/CoAl-HT exhibited preferable activity and selectivity towards styrene oxide (72% selectivity at 99.5% styrene conversion) due to its high dispersion of CuO and surface area of Cu. The improved dispersion of CuO/CoAl-HT could be ascribed to the nature of HT support, especially the synergistic effect of acidic and basic sites on the surface, which facilitated the formation of highly dispersed CuO species. A structure-performance relationship study indicated that copper(ii) in CuO was the active site for the epoxidation and oxidation of styrene, and that Cu of rich electronic density favored the improvement of selectivity of styrene oxide. Based on these results, a reaction mechanism was proposed. Moreover, the preferred catalytic performance of CuO/CoAl-HT could be maintained in five reused cycles.

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