ArticleInternational journal of nanomedicine2025
Intravenous Delivery of Angiopep-Functionalized Polypropylenimine Dendriplex Enhances Gene Expression in the Brain.
Article in International journal of nanomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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