The long term objective of this project is to prepare a protein-based drug carrier that can be used in drug targeting to solid tumors. Macromolecules are shown to accumulate in leaky blood vessels surrounding rapidly growing tumor tissue. However, the movement of these molecules from where they are retained to actual tumor cells is extremely slow, due to unfavorable convection, or solvent drag, around the tumor site. In contrast, small molecules (<10 kDa)can utilize diffusion dictated by concentration gradient to access the site of action. The overall goals of the proposed study are to: (1) synthesize water-soluble biotinylated derivative of paclitaxel, (2) identify high-affinity paclitaxel-binding proteins via the mRNA display system, (3) further select those that will release paclitaxel when pH is lowered to 6.5 or temperature is elevated to 42?C, (4) covalently couple these proteins to a dendrimer to increase the overall MW, and (5) finally characterize the assembly in terms of paclitaxel binding and release.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA119938-02
Application #
7128097
Study Section
Special Emphasis Panel (ZRG1-ONC-P (29))
Program Officer
Bini, Alessandra M
Project Start
2006-01-01
Project End
2009-04-30
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$29,218
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Watson, Venita Gresham; Hardison, Nicholas E; Harris, Tyndall et al. (2011) Genomic profiling in CEPH cell lines distinguishes between the camptothecins and indenoisoquinolines. Mol Cancer Ther 10:1839-45
Watson, Venita Gresham; Motsinger-Reif, Alison; Hardison, Nicholas E et al. (2011) Identification and replication of loci involved in camptothecin-induced cytotoxicity using CEPH pedigrees. PLoS One 6:e17561
Gresham, Venita; McLeod, Howard L (2009) Genomics: applications in mechanism elucidation. Adv Drug Deliv Rev 61:369-74