Two-Step Mechanism of Cellular Uptake of Cationic Gold Nanoparticles Modified by (16-Mercaptohexadecyl)trimethylammonium Bromide
Language English Country United States Media print-electronic
Document type Journal Article
- MeSH
- Cell Membrane drug effects metabolism MeSH
- Endocytosis drug effects physiology MeSH
- Exocytosis * drug effects physiology MeSH
- Microscopy, Confocal MeSH
- Culture Media MeSH
- Quaternary Ammonium Compounds chemical synthesis chemistry MeSH
- Humans MeSH
- Lysosomes drug effects MeSH
- Microscopy, Electron, Scanning MeSH
- Cell Line, Tumor MeSH
- Nanotubes analysis chemistry MeSH
- Polylysine chemistry pharmacokinetics MeSH
- Cell Proliferation drug effects MeSH
- Proteoglycans chemistry metabolism MeSH
- Flow Cytometry MeSH
- Drug Stability MeSH
- Sulfhydryl Compounds chemistry MeSH
- Chemistry Techniques, Synthetic MeSH
- Gold chemistry pharmacokinetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- (16-mercaptohexadecyl)trimethylammonium bromide MeSH Browser
- cationic colloidal gold MeSH Browser
- Culture Media MeSH
- Quaternary Ammonium Compounds MeSH
- Polylysine MeSH
- Proteoglycans MeSH
- Sulfhydryl Compounds MeSH
- Gold MeSH
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), MTABGNRs, 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 MTABGNRs 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, MTABGNRs were diluted equally and relatively rapidly into daughter cells; however, in nondividing/senescent cells the loss of MTABGNRs was gradual and very modest, attributable mainly to exocytosis. Exocytosed MTABGNRs 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.
Biomedical Research Center University Hospital CZ 500 05 Hradec Kralove Czech Republic
Genome Integrity Unit Danish Cancer Society Research Center DK 2100 Copenhagen Denmark
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