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.
Keywords: Cytochrome P450; Gold nanoparticles; Human liver microsomes; Human plasma protein corona; Individual variation; Testosterone metabolism.