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.

Cell membrane coating has recently emerged as a promising biomimetic approach to engineering nanoparticles (NPs) for targeted drug delivery. However, simple cell membrane coating may not meet the need for efficient drug delivery to the brain. Here, a novel molecular engineering strategy to modify the surface of NPs with a cell membrane coating for enhanced brain penetration is reported. By using poly(lactic‐co‐glycolic) acid NPs as a model, it is shown that delivery of NPs to the ischemic brain is enhanced through surface coating with the membrane of neural stem cells (NSCs), and the delivery efficiency can be further increased using membrane isolated from NSCs engineered for overexpression of CXCR4. It is found that this enhancement is mediated by the chemotactic interaction of CXCR4 with SDF‐1, which is enriched in the ischemic microenvironment. It is demonstrated that the resulting CXCR4‐overexpressing membrane‐coated NPs, termed CMNPs, significantly augment the efficacy of glyburide, an anti‐edema agent, for stroke treatment. The study suggests a new approach to improving drug delivery to the ischemic brain and establishes a novel formulation of glyburide that can be potentially translated into clinical applications to improve management of human patients with stroke.

Stroke is a deadly disease without effective pharmacotherapies, which is due to two major reasons. First, most therapeutics cannot efficiently penetrate the brain. Second, single agent pharmacotherapy may be insufficient and effective treatment of stroke requires targeting multiple complementary targets. Here, we set to develop single component, multifunctional nanoparticles (NPs) for targeted delivery of glyburide to the brain for stroke treatment.Methods: To characterize the brain penetrability, we radiolabeled glyburide, intravenously administered it to stroke- bearing mice, and determined its accumulation in the brain using positron emission tomography-computed tomography (PET/CT). To identify functional nanomaterials to improve drug delivery to the brain, we developed a chemical extraction approach and tested it for isolation of nanomaterials from E. ulmoides, a medicinal herb. To assess the therapeutic benefits, we synthesized glyburide-loaded NPs and evaluated them in stroke- bearing mice.Results: We found that glyburide has a limited ability to penetrate the ischemic brain. We identified betulinic acid (BA) capable of forming NPs, which, after intravenous administration, efficiently penetrate the brain and significantly reduce ischemia-induced infarction as an antioxidant agent. We demonstrated that BA NPs enhance delivery of glyburide, leading to therapeutic benefits significantly greater than those achieved by either glyburide or BA NPs.Conclusion: This study suggests a new direction to identify functional nanomaterials and a simple approach to achieving anti-edema and antioxidant combination therapy. The resulting glyburide- loaded BA NPs may be translated into clinical applications to improve clinical management of stroke.

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The treatment of glioblastoma has been a big challenge for decades in the oncological field mainly owing to its unique biological characteristics, such as high heterogeneity, diffusing invasiveness, and capacity to resist conventional therapies. The mRNA-based therapeutic modality holds many superior features, including easy manipulation, rapid and transient expression, and adaptive convertibility without mutagenesis, which are suitable for dealing with glioblastoma's complexity and variability. Synthetic anticancer mRNAs carried by various vehicles act as the ultimate attackers of the tumor across biological barriers. In this modality, specifically targeted glioblastoma treatment can be guaranteed by adding targeting molecules at certain levels. The choice of mRNA-bearing vehicle and administration method is a fully patient-tailored selection. This review covers the advantages and possible limitations of mRNA-based gene therapy, the in vitro synthesis of mRNA, the feasible methods for synthetic mRNA delivery and clinical therapeutic prospects of mRNA-based gene therapy for glioblastoma.

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In recent years, there has been a trend for increased incidence of cerebral schistosomiasis. It is often misdiagnosed because of the diversity of clinical symptoms. We wished to explore clinical characteristics and imaging findings in cerebral schistosomiasis. We retrospectively analyzed clinical data, laboratory tests, CT, and MRI results in 11 patients with cerebral schistosomiasis. All patients had chronic cerebral schistosomiasis (five with epilepsy type, five with brain tumor type, and one patient with stroke type). All patients with brain tumor type were misdiagnosed as having gliomas. There were typical findings on CT and MRI. In conclusion, clinical manifestations of cerebral schistosomiasis are variable, and the rate of misdiagnosis is high. For more precise diagnosis, a combination of laboratory and imaging data is required.