Nanoparticle-Mediated Rescue of p53 Through Targeted Degradation of MDM2
Annual summary rept. 18 Aug 2004-17 Aug 2005
MASSACHUSETTS UNIV AMHERST
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The interaction between MDM2 and p53 is a viable therapeutic target, as overexpression of MDM2 can lead to excessive p53 degradation, suppressing a cells ability to cope with cellular insult. The goal of this research is to use recent advances in nanotechnology to develop a specific nanoparticle antagonist to disrupt the MDM2p53 interaction. Inhibiting the interaction between p53 and MDM2 allows wild-type p53 concentrations to rise to functional levels, effectively killing proliferating tumor cells. By incorporating traditional peptide inhibitors of MDM2 with mixed-monolayer protected gold cluster nanoparticles, we hope to effect MDM2 denaturation on the nanoparticle surface, increase peptide stability, and facilitate intracellular peptide delivery. Nanoparticle characteristics, such as size, surface chemistry and biocompatibility, may be controlled and modified for these specific applications. Preliminary research demonstrated that nanoparticle- peptide conjugates can indeed inhibit MDM2. In the second year of the research grant, certain aspects of nanoparticle and peptide design were addressed to facilitate purification and quantification of the nanoparticle-peptide conjugates. These studies are necessary to validate the preliminary findings of inhibition.
- Medicine and Medical Research