Cationic colloidal gold nanorods (GNRs) have a great potential as a theranostic tool for diverse medical applications. GNRs' properties such as cellular internalization and stability are determined by physicochemical characteristics of their surface coating. GNRs modified by (16-mercaptohexadecyl)trimethylammonium bromide (MTAB), GNRs, show excellent cellular uptake. Despite their promise for biomedicine, however, relatively little is known about the cellular pathways that facilitate the uptake of GNRs, their subcellular fate and intracellular persistence. Here we studied the mechanism of cellular internalization and long-term fate of GNRs coated with MTAB, for which the synthesis was optimized to give higher yield, in various human cell types including normal diploid versus cancerous, and dividing versus nondividing (senescent) cells. The process ofGNRs internalization into their final destination in lysosomes proceeds in two steps: (1) fast passive adhesion to cell membrane mediated by sulfated proteoglycans occurring within minutes and (2) slower active transmembrane and intracellular transport of individual nanorods via clathrin-mediated endocytosis and of aggregated nanorods via macropinocytosis. The expression of sulfated proteoglycans was the major factor determining the extent of uptake by the respective cell types. Upon uptake into proliferating cells, GNRs were diluted equally and relatively rapidly into daughter cells; however, in nondividing/senescent cells the loss ofGNRs was gradual and very modest, attributable mainly to exocytosis. Exocytosed GNRs can again be internalized. These findings broaden our knowledge about cellular uptake of gold nanorods, a crucial prerequisite for future successful engineering of nanoparticles for biomedical applications such as photothermal cancer therapy or elimination of senescent cells as part of the emerging rejuvenation approach.
In this work, incubations of testosterone, dehydroepiandrosterone and pregnenolone with Mucor hiemalis MRC 70325 have been reported. Incubation of testosterone afforded androst-4-en-3,17-dione (3%), 14α-hydroxyandrost-4-en-3,17-dione (9%), 6β-hydroxyandrost-4-en-3,17-dione (2%) and 14α,17β-dihydroxyandrost-4-en-3-one (62%). Incubation of dehy droepiandrosterone afforded 3β,17β-dihydroxyandrost-5-ene (6%) and 3β,7α-dihydroxyandrost-5en-17-one (72%). Incubation of pregnenolone afforded 3β,14α-dihydroxypregn-5-en-7,20-dione (3%), 3β,7α-dihydroxypregn-5-en-20-one (64%) and 3β,7α,11α-trihydroxypregn-5-en-20-one (11%). 3β,14α-Dihydroxypregn-5-en-7,20-dione was identified as a new metabolite.
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