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Characterization of Free and Porous Silicon-Encapsulated Superparamagnetic Iron Oxide Nanoparticles as Platforms for the Development of Theranostic Vaccines

机译:表征的游离和多孔硅包裹的超顺磁性氧化铁纳米粒子作为发展治疗疫苗的平台

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摘要

Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on the influence of vaccine components on particle and immune cell trafficking and therapeutic efficacy. In this study, we create a hybrid particle vaccine platform comprised of porous silicon (pSi) and superparamagnetic iron oxide nanoparticles (SPIONs). The impact of nanoparticle size and mode of presentation on magnetic resonance contrast enhancement are examined. SPION-enhanced relaxivity increased as the core diameter of the nanoparticle increased, while encapsulation of SPIONs within a pSi matrix had only minor effects on T2 and no significant effect on T2* relaxation. Following intravenous injection of single and hybrid particles, there was an increase in negative contrast in the spleen, with changes in contrast being slightly greater for free compared to silicon encapsulated SPIONs. Incubation of bone marrow-derived dendritic cells (BMDC) with pSi microparticles loaded with SPIONs, SIINFEKL peptide, and lipopolysaccharide stimulated immune cell interactions and interferon gamma production in OT-1 TCR transgenic CD8+ T cells. Overall, the hybrid particle platform enabled presentation of a complex payload that was traceable, stimulated functional T cell and BMDC interactions, and resolved in cellular activation of T cells in response to a specific antigen.
机译:追踪疫苗成分从注射部位到淋巴组织中的目的地,并同时监测免疫效果,阐明了疫苗成分对颗粒和免疫细胞运输以及治疗功效的影响。在这项研究中,我们创建了由多孔硅(pSi)和超顺磁性氧化铁纳米颗粒(SPIONs)组成的混合颗粒疫苗平台。检查了纳米颗粒大小和呈现方式对磁共振对比增强的影响。 SPION增强的弛豫性随纳米颗粒的核心直径的增加而增加,而将SPION封装在pSi基质中对T2的影响很小,而对T2 *的松弛没有明显的影响。静脉内注射单个和混合颗粒后,脾脏的负对比度增加,与硅包封的SPION相比,游离的对比度变化略大。载有SPIONs,SIINFEKL肽和脂多糖的pSi微粒在骨髓源性树突状细胞(BMDC)中孵育,可刺激OT-1 TCR转基因CD8 + T细胞中的免疫细胞相互作用和干扰素γ的产生。总的来说,混合粒子平台能够呈现复杂的有效载荷,该有效载荷是可追踪的,刺激了功能性T细胞和BMDC相互作用,并在响应特定抗原的T细胞的细胞活化中得以解决。

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