Targeting Paclitaxel-Loaded Nanoparticles to Ovarian Cancer
Revised final rept. 1 May 2009-30 Apr 2013
CALIFORNIA UNIV SAN DIEGO LA JOLLA
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The specific aims of this project are to 1 determine the efficacy, pharmacokinetics, toxicology and imaging capacity of RGDtargeted Nexil and, 2 determine the ability of other ovarian cancer-specific targeting ligands to enhance the efficacy of Nexil. Substantial progress has been made on both of these specific aims. This is the final report. We have established that there is an excellent correlation between the tumor uptake of Nexil and its ability to deliver paclitaxel in a panel of 8 human tumor xenografts. Although we successfully synthesized RGD-target Nexil we were unable to show improved efficacy in a lung cancer mode. We have shown that the CPE peptide effectively targets the toxin gelonin to human ovarian cancer cells in a claudindependent manner, but that this fusion molecule has a difficult time getting out of the endosomal compartment and reaching the ribosome which is the target of gelonin. We have identified the A6 peptide as a CD44 tumor-targeting peptide worthy of further study.
- Medicine and Medical Research