PDF(Pubmed)
Abstract：
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.
摘要：
中风是导致死亡和残疾的主要原因。目前,这种疾病没有有效的药物治疗方法，这可以部分归因于无法有效地向大脑提供治疗。在这里，我们报告了天然化合物衍生的纳米颗粒（NPs）的发展，它既可以作为中风治疗的有效治疗剂，又可以作为向缺血性大脑输送药物的有效载体。首先,我们筛选了一组天然纳米材料,并确定了桦木酸(BA)是治疗中风最有效的抗氧化剂之一.接下来,我们设计了BANP,通过将BA化学转化为桦木胺(BAM),在酸性缺血组织中优先释放药物,并通过CXCR4拮抗剂AMD3100的表面缀合进行靶向药物递送。所得的AMD3100-共轭BAMNP，或A-BAMNP，然后被评估为用于中风治疗的治疗剂和作为用于递送神经保护肽NA1的载体。我们表明，A-BAMNP的静脉给药有效地改善了中风的恢复，并且当NA1被封装时，其功效进一步增强。由于它们的多功能性和显著的功效，我们预计,A-BAMNP有可能同时作为治疗药物和药物载体来改善卒中的治疗.
