Choi Kyoungju, Joo Hyun
Department of Anatomy & Physiology, Nanotechnology Innovation Center of Kansas State (NICKS), College of Veterinary Medicine, Kansas State University, Manhattan, KS, 66506, USA.
Nanoscale Res Lett. 2019 Jun 17;14(1):205. doi: 10.1186/s11671-019-3021-z.
Gold nanoparticle (AuNP)-protein corona complexes can alter cytochrome P450 (CYP)-mediated testosterone (TST) metabolism by altering their physicochemical properties. We investigated the impact of NP size, surface chemistry, and protein corona in TST metabolism in pooled human liver microsomes (pHLM) employing 40 and 80 nm AuNP functionalized with branched polyethylenimine (BPEI), lipoic acid (LA), and polyethylene glycol (PEG) as well as human plasma protein corona (PC). Individual variation in AuNP-mediated TST metabolism was also characterized among single donor HLM that contained different levels of CYP activities. Inhibitory effects of 40 nm AuNP and to a lesser degree of 80 nm AuNP occurred for the production of a total of five hydroxylated metabolites of TST in pHLM but PC alleviated them. Meanwhile, naked AuNP increased androstenedione production. Interindividual variation in TST metabolism occurred within single donor HLM. In most cases, 40 and 80 nm naked and PC AuNP essentially suppressed TST metabolism at non-inhibitory concentration but PC PEG-AuNP increased androstenedione. These studies contribute to a better understanding of the role of AuNP as TST disruptor by altering TST metabolism and could be utilized to screen other NP as potential endocrine disruptor.
金纳米颗粒（AuNP）-蛋白质冠复合物可通过改变其物理化学性质来改变细胞色素P450（CYP）介导的睾酮（TST）代谢。我们使用用支化聚乙烯亚胺（BPEI）、硫辛酸（LA）和聚乙二醇（PEG）功能化的40和80纳米AuNP以及人血浆蛋白冠（PC），研究了纳米颗粒大小、表面化学和蛋白质冠对人肝微粒体（pHLM）中TST代谢的影响。还对含有不同水平CYP活性的单个供体肝微粒体中AuNP介导的TST代谢的个体差异进行了表征。40纳米AuNP对pHLM中总共五种TST羟基化代谢产物的产生有抑制作用，80纳米AuNP的抑制作用较小，但PC可减轻这些抑制作用。同时，裸AuNP增加了雄烯二酮的产生。单个供体肝微粒体中TST代谢存在个体间差异。在大多数情况下，40和80纳米的裸AuNP和PC AuNP在非抑制浓度下基本抑制TST代谢，但PC PEG-AuNP增加了雄烯二酮的产生。这些研究有助于更好地理解AuNP通过改变TST代谢作为TST干扰物的作用，并可用于筛选其他纳米颗粒作为潜在的内分泌干扰物。
