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多室脂质多聚体作为疫苗制剂中抗原和基因递送的载体。

Multicompartmental Lipopolyplex as Vehicle for Antigens and Genes Delivery in Vaccine Formulations.

作者信息

Sanmartín Isaías, Sendra Luis, Moret Inés, Herrero María José, Aliño Salvador F

机构信息

Faculty of Veterinary and Experimental Sciences, Universidad Católica de Valencia, 46001 Valencia, Spain.

Pharmacology Department, Faculty of Medicine, Universidad de Valencia, 46010 Valencia, Spain.

出版信息

Pharmaceutics. 2021 Feb 19;13(2):281. doi: 10.3390/pharmaceutics13020281.

DOI:10.3390/pharmaceutics13020281
PMID:33669785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7922173/
Abstract

Vector design and its characterization is an area of great interest in current vaccine research. In this article, we have formulated and characterized a multicompartmental lipopolyplex, which associates multiple liposomes and polyplexes in the same complex. These particles allow the simultaneous delivery of lipid or water-soluble antigens associated with genes to the same cell, in much higher amounts than conventional lipopolyplexes. The vector characterization and optimization were carried out using liposomes with entrapped carboxyfluorescein and adapted electrophoretic assays. Two types of lipopolyplexes (containing hydrophilic or lipophilic antigens) were employed to evaluate their interest in vaccination. The lipopolyplex loaded with an extract of water-soluble melanoma proteins proved to efficiently induce humoral response in murine melanoma model, increasing the levels of IgM and IgG. The specificity of the immune response induced by the lipopolyplex was demonstrated in mice with the lipopolyplex containing the GD3 ganglioside lipid antigen, abundant in melanoma cells. The levels of anti-GD3 IgG increased markedly without modifying the expression of humoral antibodies against other gangliosides.

摘要

载体设计及其特性表征是当前疫苗研究中备受关注的领域。在本文中,我们构建并表征了一种多室脂质多聚体,它在同一复合物中结合了多个脂质体和多聚体。这些颗粒能够将与基因相关的脂质或水溶性抗原同时递送至同一细胞,其递送量比传统脂质多聚体高得多。使用包裹有羧基荧光素的脂质体和改良的电泳分析方法对载体进行表征和优化。采用两种类型的脂质多聚体(含有亲水性或亲脂性抗原)来评估它们在疫苗接种方面的价值。负载水溶性黑色素瘤蛋白提取物的脂质多聚体在小鼠黑色素瘤模型中被证明能有效诱导体液免疫反应,提高IgM和IgG水平。在含有黑色素瘤细胞中丰富的GD3神经节苷脂脂质抗原的脂质多聚体的小鼠中,证明了脂质多聚体诱导的免疫反应的特异性。抗GD3 IgG水平显著升高,而针对其他神经节苷脂的体液抗体表达未发生改变。

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Molecules. 2020 Jul 18;25(14):3277. doi: 10.3390/molecules25143277.
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Codelivery of mRNA with α-Galactosylceramide Using a New Lipopolyplex Formulation Induces a Strong Antitumor Response upon Intravenous Administration.使用新型脂质多聚体配方将mRNA与α-半乳糖神经酰胺共同递送,静脉注射后可诱导强烈的抗肿瘤反应。
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