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羧甲基-β-葡聚糖/壳聚糖纳米粒:新型耐热且高效的抗原传递载体。

Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery.

机构信息

Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), School of Pharmacy, Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Campus Vida, Santiago de Compostela, 15706, Spain.

Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.

出版信息

Drug Deliv Transl Res. 2021 Aug;11(4):1689-1702. doi: 10.1007/s13346-021-00968-9. Epub 2021 Apr 1.

Abstract

In the last few decades, nanotechnology has emerged as an important tool aimed at enhancing the immune response against modern antigens. Nanocarriers designed specifically for this purpose have been shown to provide protection, stability, and controlled release properties to proteins, peptides, and polynucleotide-based antigens. Polysaccharides are particularly interesting biomaterials for the construction of these nanocarriers given their wide distribution among pathogens, which facilitates their recognition by antigen-presenting cells (APCs). In this work, we focused on an immunostimulant beta-glucan derivative, carboxymethyl-β-glucan, to prepare a novel nanocarrier in combination with chitosan. The resulting carboxymethyl-β-glucan/chitosan nanoparticles exhibited adequate physicochemical properties and an important protein association efficiency, with ovalbumin as a model compound. Moreover, thermostability was achieved through the optimization of a lyophilized form of the antigen-loaded nanoparticles, which remained stable for up to 1 month at 40 ºC. Biodistribution studies in mice showed an efficient drainage of the nanoparticles to the nearest lymph node following subcutaneous injection, and a significant co-localization with dendritic cells. Additionally, subcutaneous immunization of mice with a single dose of the ovalbumin-loaded nanoparticles led to induced T cell proliferation and antibody responses, comparable to those achieved with alum-adsorbed ovalbumin. These results illustrate the potential of these novel nanocarriers in vaccination.

摘要

在过去几十年中,纳米技术已成为一种重要的工具,旨在增强对现代抗原的免疫反应。专门为此目的设计的纳米载体已被证明可提供蛋白质、肽和基于多核苷酸的抗原的保护、稳定性和控制释放特性。鉴于多糖广泛分布于病原体中,这使其易于被抗原呈递细胞 (APC) 识别,因此它们是构建这些纳米载体的特别有趣的生物材料。在这项工作中,我们专注于一种免疫刺激剂β-葡聚糖衍生物羧甲基-β-葡聚糖,与壳聚糖结合制备新型纳米载体。所得的羧甲基-β-葡聚糖/壳聚糖纳米颗粒表现出适当的物理化学性质和重要的蛋白质结合效率,以卵清蛋白为模型化合物。此外,通过优化载抗原纳米颗粒的冻干形式实现了热稳定性,在 40°C 下可稳定长达 1 个月。在小鼠中的分布研究表明,皮下注射后,纳米颗粒可有效引流至最近的淋巴结,并且与树突状细胞显著共定位。此外,单次皮下免疫接种载有卵清蛋白的纳米颗粒可诱导 T 细胞增殖和抗体反应,与吸附在明矾上的卵清蛋白相当。这些结果说明了这些新型纳米载体在疫苗接种中的潜力。

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