1. Introduction
1. The general problem of cell entry
2. Choosing modes of cell entry
3. How does Nature do it? (biomimetics)
2. Non-specific uptake mechanisms
1. Pinocytosis by all cells
2. Phagocytosis by some cells
3. Receptor mediated uptake
1. Receptor mediated transport of desired molecules
2. Example- transferrin receptor transport of iron for metabolism
4. Nanoparticle uptake
1. Size matters
2. Agglomeration reduces uptake
5. Drug delivery by "shedding"
1. Extracellular drug delivery by shedding
2. Intracellular drug release by shedding

• General reference: Alberts et al., Molecular Biology of the Cell. Garland Science 4th Edition, New York, pp. 747-756. 2002.
• Becker, C., Hodenius, M., Blendingera, G., Sechi, A., Hieronymus, T., Müller-Schulte, D., Schmitz-Rode, T., Zenke, M. “Uptake of magnetic nanoparticles into cells for cell tracking.” Journal of Magnetism and Magnetic Materials Volume 311(1): 234-237, 2007.
• Dawson, G.F., Halbert, G.W. “The In Vitro Cell Association of Invasin Coated Polylactide-Co-Glycolide Nanoparticles.” Pharmaceutical Research, Vol. 17, No. 11, 1420-1425, 2000
• Limbach, L., Yuchun, L., Grass, R.N., Brunner, T., Hintermann, M.A., Muller, M., Gunther, D., Stark, W.J. “Oxide Nanoparticle Uptake in Human Lung Fibroblasts: Effects of Particle Size, Agglomeration, and Diffusion at Low Concentrations.” Environ. Sci. Technol. 39: 9370-9376, 2005.
• Medina, C., Santos-Martinez, M.J., Radomski, A., Corrigan, O.I., Radomski1, M.W. “Nanoparticles: pharmacological and toxicological significance.” British Journal of Pharmacology 150, 552–558, 2007
• Mousavi, S.A., Malerod, L., Berg, T., Kjeken, R. “REVIEW ARTICLE: Clathrin-dependent endocytosis.” Biochemical Journal Immediate Publication. Published on 23 Sep 2003 as manuscript BJ20031000
• Nori, A., Kopecek, J. “Intracellular targeting of polymer-bound drugs for cancer chemotherapy.” Advanced Drug Delivery Reviews 57: 609– 636, 2005
• Romberg, B., Hennink, W.E., Storm, G.. “Sheddable Coatings for Long-Circulating Nanoparticles.” Pharmaceutical Research DOI: 10.1007/s11095-007-9348-7, 2007

Researchers should cite this work as follows:

• James Leary (2007), "BME 695N Lecture 7: Normal & facilitated cell entry mechanisms," http://nanohub.org/resources/3241.

1. biomedical engineering 1
2. course lecture 1
3. nanomedicine 1