National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad 38000, Punjab, Pakistan; Department of Biochemistry and Biotechnology, Faculty of Veterinary and Animal Sciences, MNS-University of Agriculture, Multan 66000, Pakistan.
National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad 38000, Punjab, Pakistan.
NanoImpact. 2022 Oct;28:100419. doi: 10.1016/j.impact.2022.100419. Epub 2022 Aug 28.
Gold nanomaterials (GNMs) have unique optical properties with less antigenicity, and their physicochemical properties have strong relation with an immunological response at bio-interface including antigenicity. An interpretation of this correlation would significantly impact on the clinical and theranostic applications of GNMs. Herein, we studied the effect of GNMs morphology on the cytotoxicity (in-vitro), innate immune responses, hepatotoxicity, and nephrotoxicity (in-vivo studies) using gold nano-cups (GNCs), porous gold nanospheres (PGNSs) and solid gold nano particles (SGNPs) coated with the same ligand to ensure similar surface chemistry. The cytotoxicity was assessed via sulfo-rhodamine B (SRB) assay, and the cytotoxicity data showed that morphological features at nanoscale dimensions like surface roughness and hollowness etc. have a significant impact on cellular viability. The biochemical and histopathological study of liver and kidney tissues also showed that all GNMs did not show any toxicity even at high concentration (100 μL). The relative quantification of cytokine gene expression of TNF-α, IFN-γ, IL-4, 1L-6, and 1L-17 (against each morphology) was checked after in-vivo activation in mice. Among the different nanogold morphologies, PVP stabilized GNCs (PVP-GNCs) showed the highest release of pro-inflammatory cytokines, which might be due to their high surface energy and large surface area for exposure as compared to other nanogold morphologies studied. The pro-inflammatory cytokine release could be suppressed by coating with some anti-inflammatory polymer, i.e., inulin. The in-vitro results of pro-inflammatory (TNF-α, IL-1) cytokines also suggested that all GNMs may induce activation of macrophages and Th1 immune response. The in-vivo activation results showed a decrease in mRNA expression of the cytokines (TNF-α, IFN-γ, IL-4, 1L-6 and 1L-17). Based on these findings, we proposed that the shape and morphology of GNMs control their immune response at nano-bio interface, and it must be considered while designing their role for different biomedical applications like immuno-stimulation and bio-imaging.
金纳米材料（GNMs）具有独特的光学特性，抗原性较低，其物理化学性质与生物界面的免疫反应密切相关，包括抗原性。对这种相关性的解释将对 GNMs 的临床和治疗应用产生重大影响。在此，我们使用金纳米杯（GNCs）、多孔金纳米球（PGNSs）和实心金纳米颗粒（SGNPs）研究了 GNMs 形态对细胞毒性（体外）、固有免疫反应、肝毒性和肾毒性（体内研究）的影响，这些纳米颗粒都涂有相同的配体以确保相似的表面化学性质。通过磺基罗丹明 B（SRB）测定法评估细胞毒性，细胞毒性数据表明，纳米尺度的形态特征，如表面粗糙度和中空等，对细胞活力有重大影响。肝和肾组织的生化和组织病理学研究也表明，即使在高浓度（100μL）下，所有 GNMs 也没有显示出任何毒性。在小鼠体内激活后，检查了 TNF-α、IFN-γ、IL-4、IL-6 和 IL-17 等细胞因子基因表达的相对定量（针对每种形态）。在不同的纳米金形态中，PVP 稳定的 GNCs（PVP-GNCs）表现出最高水平的促炎细胞因子释放，这可能是由于其高表面能和较大的暴露表面积与研究的其他纳米金形态相比。通过用一些抗炎聚合物（如菊粉）进行涂层，可以抑制促炎细胞因子的释放。体外促炎（TNF-α、IL-1）细胞因子的结果也表明，所有 GNMs 可能诱导巨噬细胞和 Th1 免疫反应的激活。体内激活结果显示细胞因子（TNF-α、IFN-γ、IL-4、IL-6 和 IL-17）的 mRNA 表达减少。基于这些发现，我们提出 GNMs 的形状和形态控制着它们在纳米生物界面的免疫反应，在设计它们用于不同的生物医学应用（如免疫刺激和生物成像）时，必须考虑到这一点。
