See references below for related reading.

4.1      Overview: targeting nanosystems to cells
4.1.1    antibody targeting
4.1.2    peptide targeting
4.1.3    aptamer targeting
4.1.4    ligand-receptor targeting

4.2      Antibodies – polyclonal and monoclonal
4.2.1    Where do antibodies come from – in nature?
4.2.2    How do we make them in the laboratory?
4.2.3    Monoclonal antibodies – some details you need to know!
4.2.4    Labeling strategies
4.2.5    Therapy problems with mouse monoclonal antibodies
4.2.6    “Humanizing” monoclonal antibodies to reduce adverse host immune reactions
4.2.7    Why antibodies may not be a good overall choices for targeting nanosystems to cells

4.3      Peptide targeting
4.3.1    How does a peptide target?
4.3.2    Examples of peptide targeting
4.3.3    Creating new peptides by random peptide phage display libraries
4.3.4    High-throughput screening of those peptide libraries
4.3.5    Advantages and disadvantages of peptide targeting

4.4      Aptamer targeting
4.4.1    What are aptamers and how do they target?
4.4.2    Some different types of aptamers
4.4.3    How do you make aptamers?
4.4.4    How do you screen for useful aptamers?

4.5      Ligand-receptor targeting
4.5.1    What are ligands?
4.5.2    What are their advantages/disadvantages?
4.5.3    Example – folate receptors

4.6      How do we quantitatively evaluate targeting?
4.6.1    Technologies for evaluating targeting
         4.6.1.1 Flow cytometry
         4.6.1.2 Scanning image cytometry
4.6.2    Evaluating targeting specificity
4.6.3    Evaluating targeting sensitivity

Leary, J.F.: "Strategies for Rare Cell Detection and Isolation" Methods in Cell Biology: Flow Cytometry (Edited by Z. Darzynkiewicz, J.P. Robinson, H.A. Crissman), vol. 42: pp. 331-358, 1994. (Full text found at nih.gov)

Leary, J.F. "Ultra High Speed Cell Sorting" Cytometry Part A 67A:76–85 (2005)

Rosenblatt, J.A., Hokanson, J.A., McLaughlin, S.R., Leary, J.F.: "A Theoretical Basis for Sampling Statistics Appropriate for the Detection and Isolation of Rare Cells Using Flow Cytometry and Cell Sorting" Cytometry 27: 233-238; 1997.(Full text found at nih.gov)

Prow, T.W., Kotov, N.A., Lvov, Y.M., Rijnbrand, R., Leary, J.F. “Nanoparticles, Molecular Biosensors, and Multispectral Confocal Microscopy” Journal of Molecular Histology, Vol. 35, No.6, pp. 555-564, 2004. (Full text found at nih.gov)

Szaniszlo, P., Rose, W.A., Wang, N., Reece, L.M., Tsulaia, T.V., Hanania, E.G., Elferink, C.J., Leary, J.F. "Scanning Cytometry with a LEAP: Laser-Enabled Analysis and Processing of Live Cells In Situ" Cytometry 69A: 641-651, 2006. (Full text found at nih.gov)

von Maltzahn, G., Ren, Y., Park, J-H, Min, D-H, Kotamraju, V.R., Jayakumar, J., Fogal, V., Sailor, M.J., Erkki Ruoslahti, E., Bhatia, S.N. "In ViVo Tumor Cell Targeting with “Click” Nanoparticles". Bioconjugate Chem. 19, 1570–1578 (2008)

McCarron,P.A., Marouf, W.M., Quinn,D.J., Fay,F., Burden,R.E., Olwill, S.A., Scott,C.J. "Antibody Targeting of Camptothecin-Loaded PLGA Nanoparticles to Tumor Cells". Bioconjugate Chem. 19, 1561–1569 (2008).

Yang, X., Bassett, S.E., Li, X., Luxon, B.A., Herzog, N.K., Shope, R.E., Aronson, J., Prow, T.W., Leary, J.F., Kirby, R., Ellington, A.D., Gorenstein, D.G.: “Construction and selection of bead bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing” Nucleic Acids Research 30 (23)e132: 1-8, 2003.

Yang, X., Li, X., Prow, T.W. Reece, L.M., Bassett, S.E., Luxon, B.A., Herzog, N.K., Aronson, J., Shope, R.E., Leary, J.F., Gorenstein, D.G. “Immunofluorescence Assay and Flow Cytometric Selection of Bead Bound Aptamers” Nucleic Acids Research 31 (10): 1-8, 2003

Ellington Lab Aptamer Database

Lu, Y., Low, P.S. "Folate-mediated delivery of macromolecular anticancer therapeutic agent". Advanced Drug Delivery Reviews 54: 675–693 (2002). (Full text found at nih.gov)

Shapiro, H.M. Practical Flow Cytometry 4th edition 2003.

Researchers should cite this work as follows:

• James Leary (2011), "BME 695L Lecture 4: Cell Targeting and its Evaluation," http://nanohub.org/resources/12056.

1. biomedical engineering 1
2. cell targeting 1
3. course lecture 1
4. nanomedicine 1