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高内涵筛选作为纳米颗粒细胞毒性指纹图谱分析的通用工具。

High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles.

作者信息

Jan Edward, Byrne Stephen J, Cuddihy Meghan, Davies Anthony M, Volkov Yuri, Gun'ko Yurii K, Kotov Nicholas A

机构信息

Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.

出版信息

ACS Nano. 2008 May;2(5):928-38. doi: 10.1021/nn7004393.

Abstract

Recent advances and progress in nanobiotechnology have demonstrated many nanoparticles (NPs) as potential and novel drug delivery vehicles, therapeutic agents, and contrast agents and luminescent biological labels for bioimaging. The emergence of new biomedical applications based on NPs signifies the need to understand, compare, and manage their cytotoxicity. In this study, we demonstrated the use of high-content screening assay (HCA) as a universal tool to probe the cytotoxicity of NPs and specifically cadmium telluride quantum dots (CdTe QDs) and gold NPs (Au NPs) in NG108-15 murine neuroblastoma cells and HepG2 human hepatocellular carcinoma cells. Neural cells represent special interest for NP-induced cytotoxicity because the optical and electrical functionalities of materials necessary for neural imaging and interfacing are matched well with the properties of many NPs. In addition, the cellular morphology of neurons is particularly suitable for automated high content screening. HepG2 cells represent a good model for high content screening studies since they are commonly used as a surrogate for human hepatocytes in pharmaceutical studies. We found the CdTe QDs to induce primarily apoptotic response in a time- and dosage-dependent manner and produce different toxicological profiles and responses in undifferentiated and differentiated neural cells. Au NPs were found to inhibit the proliferation and intracellular calcium release of HepG2 cells.

摘要

纳米生物技术的最新进展表明,许多纳米颗粒(NPs)可作为潜在的新型药物递送载体、治疗剂、造影剂以及用于生物成像的发光生物标记物。基于纳米颗粒的新生物医学应用的出现,意味着需要了解、比较和管理它们的细胞毒性。在本研究中,我们展示了使用高内涵筛选分析(HCA)作为一种通用工具,来探究纳米颗粒特别是碲化镉量子点(CdTe QDs)和金纳米颗粒(Au NPs)对NG108-15小鼠神经母细胞瘤细胞和HepG2人肝癌细胞的细胞毒性。神经细胞对于纳米颗粒诱导的细胞毒性具有特殊意义,因为神经成像和接口所需材料的光学和电学功能与许多纳米颗粒的特性非常匹配。此外,神经元的细胞形态特别适合自动化高内涵筛选。HepG2细胞是高内涵筛选研究的良好模型,因为它们在药物研究中通常被用作人类肝细胞的替代物。我们发现CdTe QDs主要以时间和剂量依赖性方式诱导凋亡反应,并在未分化和分化的神经细胞中产生不同的毒理学特征和反应。发现Au NPs可抑制HepG2细胞的增殖和细胞内钙释放。

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