Mechanisms of the immune response cause by cationic and anionic surface functionalized cellulose nanocrystals using cell-based assays
Mechanisms of the immune response cause by cationic and anionic surface functionalized cellulose nanocrystals using cell-based assays
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DOI：
10.1016/j.tiv.2018.12.009
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发表时间：
2019-03-01
影响因子：
3.2
通讯作者：
Ckless, Karina
中科院分区：
文献类型：
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作者：
Despres, Hannah W.;Sabra, Adham;Ckless, Karina
近年来，功能化纤维素纳米晶体（CNCs）在生物医学领域的应用越来越受到人们的关注。CNC适合于用一系列聚合物官能化，产生具有不同形态、表面电荷的化学相关纳米材料，这些纳米材料可以影响生物活性，包括免疫反应。在这项研究中，我们试图了解功能化的CNCs引起的免疫反应的机制差异，以及表面电荷是否在这种效果中发挥作用。我们研究了阳离子型CNCs-聚（APMA）和阴离子型CNCs-聚（NIPAAm）衍生物对人类和海洋炎症细胞分泌炎性细胞因子、线粒体源性ROS和线粒体功能和抗氧化反应以及内质网（ER）应激的影响。阳离子CNCs-聚（APMA）在小鼠细胞系中引起更强的免疫应答，而阴离子CNCs-聚（NIPAAm）在人单核细胞中显示出显著的NLRP 3炎性小体依赖性和非依赖性免疫应答。此外，CNCs-poly（NlPAAm）在未刺激的细胞中诱导更多的酸性囊泡细胞器和线粒体ROS的形成，而CNCs-poly（APMA）主要通过降低细胞内ATP来影响线粒体功能。这种生物学效应的差异可能与CNCs表面电荷的不同以及它们与细胞内和细胞外生物分子的相互作用有关。
The interest in functionalized cellulose nanocrystals (CNCs) for multiple biomedical application has been increasing in recent years. CNCs are suitable to functionalization with an array of polymers, generating chemically related nanomaterials with different morphologies, surface charges that can affect bioreactivity, including immune response. In this study, we sought to understand the mechanistic differences regarding immunological responses evoked by functionalized CNCs and whether surface charges play a role in this effect. We investigated the effect of a cationic, CNCs-poly(APMA), and an anionic, CNCs-poly(NIPAAm) derivatives 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 marine inflammatory cells. The cationic CNCs-poly (APMA) evoked a more robust immunological response in murine cell line, while the anionic CNCs-poly (NIPAAm) showed a significant NLRP3 inflammasome-dependent and independent immunological response in human monocytes. Moreover, CNCs-poly(NlPAAm) induced greater formation of acidic vesicular organelles, mitochondrial ROS in non-stimulated cells while CNCs-poly(APMA) mainly affected mitochondrial function by decreasing the intracellular ATP. The differences on the biological responses may be related to the surface charges of CNCs, and their likely interactions with intra and extracellular biomolecules.