药理学
白桦酸
药物输送
药品
冲程(发动机)
神经保护
靶向给药
医学
材料科学
纳米技术
生物
遗传学
机械工程
工程类
作者
Shenqi Zhang,Bin Peng,Zeming Chen,Jiang Yu,Gang Deng,Youmei Bao,Chao Ma,F. Du,Wendy C. Sheu,W. Taylor Kimberly,J. Marc Simard,Daniel Coman,Qianxue Chen,Fahmeed Hyder,Jiangbing Zhou,Kevin N. Sheth
标识
DOI:10.1016/j.bioactmat.2022.02.033
摘要
Stroke is the leading cause of death and disability. Currently, there is no effective pharmacological treatment for this disease, which can be partially attributed to the inability to efficiently deliver therapeutics to the brain. Here we report the development of natural compound-derived nanoparticles (NPs), which function both as a potent therapeutic agent for stroke treatment and as an efficient carrier for drug delivery to the ischemic brain. First, we screened a collection of natural nanomaterials and identified betulinic acid (BA) as one of the most potent antioxidants for stroke treatment. Next, we engineered BA NPs for preferential drug release in acidic ischemic tissue through chemically converting BA to betulinic amine (BAM) and for targeted drug delivery through surface conjugation of AMD3100, a CXCR4 antagonist. The resulting AMD3100-conjugated BAM NPs, or A-BAM NPs, were then assessed as a therapeutic agent for stroke treatment and as a carrier for delivery of NA1, a neuroprotective peptide. We show that intravenous administration of A-BAM NPs effectively improved recovery from stroke and its efficacy was further enhanced when NA1 was encapsulated. Due to their multifunctionality and significant efficacy, we anticipate that A-BAM NPs have the potential to be translated both as a therapeutic agent and as a drug carrier to improve the treatment of stroke.
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