<p>Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles</p>

Abstract

Background: Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated. Purpose: The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo. Results: Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice. Conclusion: Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.

Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

“…It is important to notice that viabilities of T731-GFP cells were slightly larger than those obtained for HeLa-GFP ones, in agreement with previous works [ 43 ]. This can be a consequence of the faster cell division cycle of T731 cells and the phenotype differences between both types of cell lines herein used [ 77 , 78 ].…”

Ultrastructural Features of Gold Nanoparticles Interaction with HepG2 and HEK293 Cells in Monolayer and Spheroids

“…We did not find any study confirming or neglecting our results. Uptake of AuNPs (20 nm) by HepG2 cells was detected by inductively coupled plasma mass spectrometry [ 26 ], however, this method did not provide reliable results because it operates with a whole mass of the cells dissolved in 3% HNO3, so it is impossible say were AuNPs inside the cells or were they adsorbed on cell surface [ 25 ]. The TEM of ultrathin sections is the only method that unambiguously demonstrates the penetration of metal NPs into cells and allows identification of cell structures without a special labeling.…”

“…Morphological changes in spheroids treated with NPs or chemical compounds are studied mainly in transmitted light and various fluorescence methods [ 9 , 19 , 20 , 21 ]. The use of electron microscopy is rare and mostly is limited to registration of NPs presence in a cell [ 22 , 23 , 24 ] or TEM-illustration of NPs used in a study [ 9 , 15 , 21 , 25 , 26 ]. However, the size of NPs requires studying their interaction with cells at subcellular level, which is realized in a transmission electron microscopy (TEM) of ultrathin sections.…”

Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

“…The first one is the available receptors on the cell membrane (e.g., folic acid and transferrin receptors), which are often overexpressed in cancer cells. The second one is non-specific absorbed proteins on the surface of NPs (e.g., α- and β-globulin proteins) [ 28 ]. These factors can determine whether and how NPs enter into the cells by CME, as well as affecting the uptake of NPs into cancer cells through multiple receptors on the cell membrane.…”