Two-Step Mechanism of Cellular Uptake of Cationic Gold Nanoparticles Modified by (16-Mercaptohexadecyl)trimethylammonium Bromide

0469671 - ÚMG 2017 RIV US eng J - Článek v odborném periodiku
Žárská, Monika - Novotný, Filip - Havel, Filip - Šrámek, Michal - Babelova, A. - Benada, Oldřich - Novotný, M. - Saran, H. - Kuca, K. - Musílek, K. - Hvězdová, Zuzana - Dzijak, Rastislav - Vančurová, Markéta - Krejčíková, Kateřina - Gabajová, Blanka - Hanzlíková, Hana - Kyjacová, Lenka - Bártek, Jiří - Proška, Jan - Hodný, Zdeněk
Two-Step Mechanism of Cellular Uptake of Cationic Gold Nanoparticles Modified by (16-Mercaptohexadecyl)trimethylammonium Bromide.
Bioconjugate Chemistry. Roč. 27, č. 10 (2016), s. 2558-2574. ISSN 1043-1802. E-ISSN 1520-4812
Grant CEP: GA ČR GA16-13967S; GA MŠMT(CZ) LO1509
Grant ostatní: OPPC(XE) CZ.2.16/3.1.00/24023
Institucionální podpora: RVO:61388971 ; RVO:68378050 ; RVO:61389013
Klíčová slova: mesenchymal stem-cells * mammalian-cells * cancer-cells * photothermal therapy * mediated endocytosis * nonphagocytic cells * optical-properties * light-scattering * senescent cells * dna-damage
Kód oboru RIV: EB - Genetika a molekulární biologie; EE - Mikrobiologie, virologie (MBU-M); CD - Makromolekulární chemie (UMCH-V)
Impakt faktor: 4.818, rok: 2016

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), (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 of (MTAB)GNRs 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, (MTAB)GNRs were diluted equally and relatively rapidly into daughter cells; however, in nondividing/senescent cells the loss of (MTAB)GNRs was gradual and very modest, attributable mainly to exocytosis. Exocytosed (MTAB)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.
Trvalý link: http://hdl.handle.net/11104/0269098