Nanobiotechnology Department, Faculty of Biosciences, Tarbiat Modares University, Tehran 14115-111, Iran.
Biophysics Department, Faculty of Biosciences, Tarbiat Modares University, Tehran 14115-111, Iran.
Cells. 2022 Jan 29;11(3):478. doi: 10.3390/cells11030478.
Inadequacy of most animal models for drug efficacy assessments has led to the development of improved in vitro models capable of mimicking in vivo exposure scenarios. Among others, 3D multicellular spheroid technology is considered to be one of the promising alternatives in the pharmaceutical drug discovery process. In addition to its physiological relevance, this method fulfills high-throughput and low-cost requirements for preclinical cell-based assays. Despite the increasing applications of spheroid technology in pharmaceutical screening, its application, in nanotoxicity testing is still in its infancy due to the limited penetration and uptake rates into 3D-cell assemblies. To gain a better understanding of gold nanowires (AuNWs) interactions with 3D spheroids, a comparative study of 2D monolayer cultures and 3D multicellular spheroids was conducted using two lung cancer cell lines (A549 and PC9). Cell apoptosis (live/dead assay), metabolic activity, and spheroid integrity were evaluated following exposure to AuNWs at different dose-time manners. Results revealed a distinct different cellular response between 2D and 3D cell cultures during AuNWs treatment including metabolic rates, cell viability, dose-response curves and, uptake rates. Our data also highlighted further need for more physiologically relevant tissue models to investigate in depth nanomaterial-biology interactions. It is important to note that higher concentrations of AuNWs with lower exposure times and lower concentrations of AuNWs with higher exposure times of 3 days resulted in the loss of spheroid integrity by disrupting cell-cell contacts. These findings could help to increase the understanding of AuNWs-induced toxicity on tissue levels and also contribute to the establishment of new analytical approaches for toxicological and drug screening studies.
大多数动物模型在药物功效评估方面的不足，导致了能够模拟体内暴露情况的改进型体外模型的发展。其中，3D 多细胞球体技术被认为是药物发现过程中很有前途的替代方法之一。除了具有生理学相关性外，这种方法还满足了临床前基于细胞的测定的高通量和低成本要求。尽管球体技术在药物筛选中的应用越来越广泛，但由于其进入 3D 细胞组装体的穿透和摄取率有限，其在纳米毒性测试中的应用仍处于起步阶段。为了更好地了解金纳米线（AuNWs）与 3D 球体的相互作用，使用两种肺癌细胞系（A549 和 PC9）对 2D 单层培养物和 3D 多细胞球体进行了比较研究。在不同的剂量-时间方式下，用 AuNWs 处理后，评估了细胞凋亡（死活检测）、代谢活性和球体完整性。结果表明，在 AuNWs 处理期间，2D 和 3D 细胞培养之间存在明显不同的细胞反应，包括代谢率、细胞活力、剂量反应曲线和摄取率。我们的数据还强调需要进一步使用更具生理学相关性的组织模型来深入研究纳米材料与生物学的相互作用。需要指出的是，较高浓度的 AuNWs 与较短的暴露时间以及较低浓度的 AuNWs 与较长的 3 天暴露时间相结合，通过破坏细胞-细胞接触导致球体完整性丧失。这些发现有助于提高对组织水平上 AuNWs 诱导的毒性的理解，也有助于为毒理学和药物筛选研究建立新的分析方法。
