Mulder Danielle, Taute Cornelius Johannes Francois, van Wyk Mari, Pretorius Pieter J
Human Metabolomics, Potchefstroom Campus, North-West University, Potchefstroom 2351, South Africa.
Nanomaterials (Basel). 2022 Mar 29;12(7):1126. doi: 10.3390/nano12071126.
Gold nanoparticles (GNPs) have shown great potential in diagnostic and therapeutic applications in diseases, such as cancer. Despite GNP versatility, there is conflicting data regarding the toxicity of their overall functionalization chemistry for improved biocompatibility. This study aimed to determine the possible genotoxic effects of functionalized GNPs in Human hepatocellular carcinoma (HepG2) cells. GNPs were synthesized and biofunctionalized with seven common molecules used for biomedical applications. These ligands were bovine serum albumin (BSA), poly(sodium 4-styrene sulfonate) (PSSNA), trisodium citrate (citrate), mercaptoundecanoic acid (MUA), glutathione (GSH), polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG). Before in vitro genotoxicity assessment, inductively coupled plasma mass spectrometry was used to determine GNP cellular internalization quantitatively, followed by cell-based assays; WST-1 to find IC 30 and ApoPercentage for apoptotic induction time-points. The effect of the GNPs on cell growth in real-time was determined by using xCELLigence, followed by a comet assay for genotoxicity determination. The HepG2 cells experienced genotoxicity for all GNP ligands; however, they were able to initiate repair mechanisms and recover DNA damage, except for two functionalization chemistries.
金纳米颗粒(GNPs)在癌症等疾病的诊断和治疗应用中已显示出巨大潜力。尽管金纳米颗粒具有多功能性,但关于其整体功能化化学以提高生物相容性的毒性数据存在矛盾。本研究旨在确定功能化金纳米颗粒对人肝癌(HepG2)细胞可能的遗传毒性作用。合成了金纳米颗粒并用七种用于生物医学应用的常见分子进行生物功能化。这些配体分别是牛血清白蛋白(BSA)、聚(4-苯乙烯磺酸钠)(PSSNA)、柠檬酸三钠(柠檬酸盐)、巯基十一烷酸(MUA)、谷胱甘肽(GSH)、聚乙烯吡咯烷酮(PVP)和聚乙二醇(PEG)。在进行体外遗传毒性评估之前,使用电感耦合等离子体质谱法定量测定金纳米颗粒的细胞内化,随后进行基于细胞的检测;使用WST-1来确定IC30以及凋亡诱导时间点的凋亡百分比。通过使用xCELLigence实时测定金纳米颗粒对细胞生长的影响,随后进行彗星试验以确定遗传毒性。所有金纳米颗粒配体都使HepG2细胞产生了遗传毒性;然而,除了两种功能化化学方法外,它们能够启动修复机制并修复DNA损伤。