spaceprovided) We have developed fluorescent nanoparticles (NP) conjugated to the anticancer natural product geldanamycin (GA) to be used initially as a molecular probe for studying the pharmacological effects of GA in live cancer cells. GA is linked to the nanoparticle via a polymer coating that a) improves mechanical and chemical stability of the fluorescent nanocrystal core, b) controls the drug loading on the surface of the nanoparticle, and c) allows unassisted intracellular delivery of fluorescent nanoparticles to tumor cells. By controlling the surface loading of the drug (from 5 to 300 molecules) we have been able to demonstrate a dose response for both drug uptake and cytotoxicity in cultured cancer cells. Geldanamycin-sensitivity in cancer cells is dependent upon two different mechanisms, Hsp90 specific recognition as well as an active uptake pathway. These two factors make geldanamycin an interesting selective probe for directing nanoparticle uptake in animal tumors. This proposal aims to define the GA-dependent cellular uptake and tumor selectivity of nanoparticles that can be used as new imaging probes or multivalent drug delivery particles.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
3F32CA123662-01S1
Application #
7493914
Study Section
Special Emphasis Panel (ZCA1-RTRB-Z (M1))
Program Officer
Grodzinski, Piotr
Project Start
2006-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$51,278
Indirect Cost
Name
Purdue University
Department
Type
Organized Research Units
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Knudsen, Giselle M; Davis, Brandon M; Deb, Shirshendu K et al. (2008) Quantification of isotope encoded proteins in 2-D gels using surface enhanced resonance Raman. Bioconjug Chem 19:2212-20
Deb, Shirshendu K; Davis, Brandon; Knudsen, Giselle M et al. (2008) Detection and relative quantification of proteins by surface enhanced Raman using isotopic labels. J Am Chem Soc 130:9624-5
Loethen, Yvette L; Knudsen, Giselle M; Davis, Brandon et al. (2008) Protein quantitation in 2-D gels using fluorescence with water Raman as an internal standard. J Proteome Res 7:1341-5