Toxicological studies of semiconductor quantum dots on immune cells.
Nanoengineered materials hold a vast promise of enabling revolutionary technologies, but also pose an emerging and potentially serious threat to human and environmental health. While there is increasing knowledge concerning the risks posed by engineered nanomaterials, significant inconsistencies exist within the current data based on the high degree of variability in the materials (e.g., synthesis method, coatings, etc) and biological test systems (e.g., cell lines, whole organism, etc). In this project, we evaluated the uptake and response of two immune cell lines (RAW macrophage and RBL mast cells) to nanocrystal quantum dots (Qdots) with different sizes and surface chemistries, and at different concentrations. The basic experimental design followed a 2 x 2 x 3 factorial model: two Qdot sizes (Qdot 520 and 620), two surface chemistries (amine 'NH{sub 2}' and carboxylic acid 'COOH'), and three concentrations (0, 1 nM, and 1 {micro}M). Based on this design, the following Qdots from Evident Technologies were used for all experiments: Qdot 520-COOH, Qdot 520-NH{sub 2}, Qdot 620-COOH, and Qdot 620-NH{sub 2}. Fluorescence and confocal imaging demonstrated that Qdot 620-COOH and Qdot 620-NH{sub 2} nanoparticles had a greater level of internalization and cell membrane association in RAW and RBL cells, respectively. From these data, a two-way interaction between Qdot size and concentration was observed in relation to the level of cellular uptake in RAW cells, and association with RBL cell membranes. Toxicity of both RBL and RAW cells was also significantly dependent on the interaction of Qdot size and concentration; the 1 {micro}M concentrations of the larger, Qdot 620 nanoparticles induced a greater toxic effect on both cell lines. The RBL data also demonstrate that Qdot exposure can induce significant toxicity independent of cellular uptake. A significant increase in TNF-{alpha} and decrease in IL-10 release was observed in RAW cells, and suggested that Qdot exposure induced a pro-inflammatory response. In contrast, significant decreases in both TNF-{alpha} and IL-4 releases were observed in RBL cells, which is indicative of a suppressed inflammatory response. The changes in cytokine release observed in RAW and RBL cells were primarily dependent on Qdot concentration and independent of size and surface chemistry. Changes in the activity of superoxide dismutase were observed in RAW, but not RBL cells, suggesting that RAW cells were experiencing oxidative stress induced by Qdot exposure. Overall, our results demonstrate that the uptake/association and biomolecular response of macrophage and mast cells is primarily driven by an interaction between Qdot size and concentration. Based on these findings, a more detailed understanding of how size directly impacts cellular interactions and response will be critical to developing predictive models of Qdot toxicity.
- Research Organization:
- Sandia National Laboratories (SNL), Albuquerque, NM, and Livermore, CA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC04-94AL85000
- OSTI ID:
- 945919
- Report Number(s):
- SAND2008-7710; TRN: US200904%%195
- Country of Publication:
- United States
- Language:
- English
Similar Records
A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation
Suppressive effects of ketamine on macrophage functions