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血管活性肠肽功能化聚丙亚胺树枝状复合物的静脉给药增强大脑中的基因表达。

Intravenous Delivery of Angiopep-Functionalized Polypropylenimine Dendriplex Enhances Gene Expression in the Brain.

作者信息

Ali-Jerman Hawraa, Somani Sukrut, Al-Quraishi Zainab, Maeyouf Khadeejah, Merkler Mirna, Gerasimou Symeon, Tate Rothwelle J, Sakata Shuzo, Mullin Margaret, Irving Craig, Anderson Graeme J, Bame Jessica R, MacKenzie Graeme, McNeill Gayle, Dufès Christine

机构信息

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK.

College of pharmacy, Health Sciences Centre, Kuwait University, Jabriya, 13110, Kuwait.

出版信息

Int J Nanomedicine. 2025 Sep 20;20:11569-11591. doi: 10.2147/IJN.S510487. eCollection 2025.

DOI:10.2147/IJN.S510487
PMID:41001105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12459624/
Abstract

BACKGROUND

The application of gene therapy for treating neurological disorders, including brain cancer, Parkinson's, and Alzheimer's disease, is significantly limited by the current shortage of gene vectors that can effectively cross the blood-brain barrier (BBB) following intravenous administration. Recent studies demonstrated that angiopep-2 can enhance the delivery of therapeutic agents across the BBB through receptor-mediated endocytosis. This study therefore explores the potential of angiopep-2-conjugated generation-3 diaminobutyric polypropylenimine (DAB) dendrimer (DAB-Ang) as nanocarrier for brain-targeted gene delivery.

METHODS

Angiopep-2 was conjugated to DAB dendrimer and evaluated in terms of DNA condensation ability, particle size, surface charge, and structural morphology. The cellular uptake was studied in vitro using bEnd.3 brain endothelial cells, and the in vivo efficacy of DAB-Ang dendriplexes for brain gene expression was evaluated in BALB/c mice following intravenous administration.

RESULTS

DAB-Ang dendrimer successfully condensed up to 90% of DNA, forming stable spherical dendriplexes with sizes under 240 nm and positive zeta potentials. In vitro, DAB-Ang dendriplex achieved a 9-fold higher cellular uptake in brain endothelial cells in comparison to the unmodified complex, predominantly through clathrin-mediated endocytosis and macropinocytosis. In vivo studies showed significantly increased gene expression in the brain following DAB-Ang dendriplex treatment, achieving 1.8-fold and 3.2-fold higher expression in comparison to DAB dendriplex and naked DNA, respectively, with minimal off-target effects.

CONCLUSION

Angiopep-2-conjugated DAB dendrimer demonstrated high specificity and efficacy in facilitating gene delivery to the brain, offering a promising platform for therapeutic applications in neurological disorders.

摘要

背景

基因疗法在治疗包括脑癌、帕金森病和阿尔茨海默病在内的神经疾病方面的应用，因目前缺乏静脉给药后能有效穿过血脑屏障（BBB）的基因载体而受到显著限制。最近的研究表明，血管活性肠肽-2（Angiopep-2）可通过受体介导的内吞作用增强治疗药物穿过血脑屏障的递送。因此，本研究探讨了血管活性肠肽-2偶联的第3代二氨基丁酸聚丙烯亚胺（DAB）树枝状大分子（DAB-Ang）作为脑靶向基因递送纳米载体的潜力。

方法

将血管活性肠肽-2偶联到DAB树枝状大分子上，并对其DNA凝聚能力、粒径、表面电荷和结构形态进行评估。使用bEnd.3脑内皮细胞在体外研究细胞摄取情况，并在静脉给药后在BALB/c小鼠中评估DAB-Ang树枝状复合物对脑基因表达的体内疗效。

结果

DAB-Ang树枝状大分子成功凝聚了高达90%的DNA，形成了大小在240 nm以下且具有正ζ电位的稳定球形树枝状复合物。在体外，与未修饰的复合物相比，DAB-Ang树枝状复合物在脑内皮细胞中的细胞摄取量高9倍，主要通过网格蛋白介导的内吞作用和巨胞饮作用。体内研究表明，DAB-Ang树枝状复合物治疗后脑中基因表达显著增加，与DAB树枝状复合物和裸DNA相比，表达分别高出1.8倍和3.2倍，且脱靶效应最小。

结论

血管活性肠肽-2偶联的DAB树枝状大分子在促进基因递送至脑方面表现出高特异性和有效性，为神经疾病的治疗应用提供了一个有前景的平台。

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3
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