- Outline – the need for single cell measures of nanotoxicity
- There is more than one way for a cell to die...
- Necrosis" vs. "Apoptosis"
- There are other forms of "toxicity"
- Some other challenges in measuring toxicity of nanomaterials
- Necrosis vs. Apoptosis mechanisms
- Necrosis is unplanned "cell injury"
- Apoptosis is planned "programmed cell death"
- Why it is important to distinguish between necrosis and apoptosis
- Single cell assays for necrosis and apoptosis
- Dye exclusion assays for necrosis
- TUNEL assays for late apoptosis
- Annexin V assays for early apoptosis
- COMET assays for DNA damage and repair
- Light scatter assays
- Nanotoxicity in vivo – some additional challenges
- Single cell nanotoxicity, plus....
- Accumulations of nanoparticles can change toxicity locally to tissues and organs
- Filtration issues of nanoparticles – size matters – toxicity to liver and lung
- Chana, W-H, Nion-Shiao, N-H, Pin-Zhen Lu, P-Z. CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. Toxicol. Lett. (2006), doi:10.1016/j.toxlet.2006.09.007
- Darzynkiewicz Z, Juan G, Li X, Gorczyca W, Murakami T, Traganos F. Cytometry in cell necrobiology: analysis of apoptosis and accidental cell death (necrosis). Cytometry. 1997 Jan 1;27(1):1-20.
- Kirchner,C. Liedl, T., Kudera, S., Pellegrino,T., Munoz Javier, A., Hermann E. Gaub,H.E., Stolzle,S., N. Fertig, Parak, W.P., Cytotoxicity of Colloidal CdSe and CdSe/ZnS Nanoparticles. Nano Lett., Vol. 5, No. 2, 331-338, 2005.
- Oberdörster,G., Oberdörster, E. Oberdörster, J. Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles. Environmental Health Perspectives 113(7): 2005
- Ryman-Rasmussen, J.P., Riviere, J.E.,Monteiro-Riviere, N.A. Surface Coatings Determine Cytotoxicity and Irritation Potential of Quantum Dot Nanoparticles in Epidermal Keratinocytes. Journal of Investigative Dermatology. 10 August 2006; doi:10.1038/sj.jid.5700508
- Shiohara, A., Hoshino, A., Hanaki, K., Suzuki, K., Yamamoto, K. On the cytotoxicity caused by quantum dots. Microbiol. Immunol. 48(9): 669-675, 2004.
Researchers should cite this work as follows:
James Leary (2007), "BME 695N Lecture 17: Assessing nanotoxicity at the single cell level," http://nanohub.org/resources/3497.
Biomedical Engineering Building, Room 1083