Cell-based analysis of the immune and antioxidant response of the nanocarrier β-cyclodextrin conjugated with cellulose nanocrystals
Cell-based analysis of the immune and antioxidant response of the nanocarrier β-cyclodextrin conjugated with cellulose nanocrystals
复制标题
基于细胞的纳米载体β-环糊精与纤维素纳米晶体缀合的免疫和抗氧化反应分析
DOI：
10.1016/j.freeradbiomed.2018.10.244
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发表时间：
2018
影响因子：
7.4
通讯作者：
Ckless, Karina
中科院分区：
文献类型：
--
作者：
Despres, Hannah;Sunasee, Rajesh;Carson, Melissa;Pacherille, Angela;Nunez, Kaylee;Ckless, Karina
近年来，人们对用于多种生物医学应用的纤维素纳米晶体（CNC）衍生物的兴趣不断增加。 CNC 是一个多功能平台，根据提取和制备方法的不同，其尺寸和分散度会发生变化，这可能会影响它们在生物系统中的反应性。此外，CNC 适合用一系列聚合物进行功能化，生成具有不同形态、表面电荷和反应性的化学相关纳米材料。这种物理化学特性的多样性可能导致各种生物活性，并可能导致不良影响，包括强烈的免疫反应。此前，我们报道了一种阳离子 CNCs 衍生物 CNCs-poly (AEMA2)，通过诱导炎症细胞因子白细胞介素-1β (IL-1β) 的分泌，在小鼠和人类巨噬细胞中引起显着的免疫反应。这种效应部分与线粒体衍生的活性物质（ROS）有关。在这项研究中，我们试图了解功能化 CNC 引起的免疫反应的机制差异，以及表面电荷是否与这种效应相关。我们研究了阳离子 CNCs-poly (AMPA) 和阴离子 CNCs-poly (NIPAAm) 衍生物对人和小鼠炎症细胞中炎症细胞因子分泌、线粒体衍生的 ROS 和线粒体功能和抗氧化反应以及内质网 (ER) 应激的影响。 CNCs-poly (AMPA) 在 LPS 刺激的小鼠细胞系中引起最大的免疫反应，而 CNCs-poly (NIPAAm) 在未刺激的人原代单核细胞中表现出显着的 NLRP3 炎性体依赖性和独立的免疫反应。此外，CNCs-poly (NI-PAAm) 增加了酸性囊泡细胞器和线粒体-ROS 的生成，并增加未刺激细胞中的抗氧化酶，而 CNCs-poly (AMPA) 通过减少细胞内 ATP 影响线粒体功能。线粒体功能和内质网应激反应的这些差异表明其免疫活性存在多种机制。此外，这些效应可能与功能化 CNC 的表面电荷及其可能与细胞内和细胞外环境中的生物分子的相互作用有关。 https://doi. org/10.1016/j。自由生物医学。 2018.10. 243
The interest in derivatives of cellulose nanocrystals (CNCs) for multiple biomedical application has been increasing in the recent years. CNCs is a versatile platform that shows variation in size and dispersion depending on the methods of extraction and preparations, which can impact their reactivity in biological systems. In addition, CNCs are suitable to functionalization with an array of polymers, generating chemically related nanomaterials with different morphologies, surface charges and reactivity. This diversity of physicochemical characteristics can lead to a various biological activities and potentially to undesirable effects, including a robust immune response. Previously, we reported that a cationic CNCs derivative, CNCs-poly (AEMA2), evoked substantial immunological response in mouse and human macrophages, by inducing the secretion of the inflammatory cytokine interleukin-1β (IL-1β). This effect was partially associated with mitochondria-derived reactive species (ROS). In this study we sought to understand the mechanistic differences regarding immunological responses evoked by functionalized CNCs and whether surface charges is associated with this effect. We investigated the effect of a cationic, CNCs-poly (AMPA), and an anionic, CNCs-poly (NIPAAm) derivative on the secretion of inflammatory cytokines, mitochondria-derived ROS and mitochondrial function and antioxidant response as well as on endoplasmic reticulum (ER) stress, in human and murine inflammatory cells. CNCs-poly (AMPA) evoked the greatest immunological response in LPS-stimulated murine cell line, while CNCs-poly (NIPAAm) showed a significant NLRP3 inflammasome-dependent and independent immunological response in non-stimulated human primary monocytes. In addition, CNCs-poly (NI-PAAm) increased the generation of acidic vesicular organelles and mitochondrial-ROS as well as increases antioxidant enzymes in non-stimulated cells, while CNCs-poly (AMPA) affected mitochondrial function by decreasing the intracellular ATP. These differences on the mitochondrial function and ER stress response suggest a diverse mechanisms associated with their immune activity. Moreover, these effects may be related with the surface charges of the functionalized CNCs, and their likely interactions with biomolecules in the intra and extracellular milieu. ht tps://doi. org/10.1016/j. freeradbiomed. 2018.10. 243