RM_SERMACS Abigail Shelton, Sujata Guha  Sunday, October 19, 2014 

1080 - Nano formulation of platin-A for cancer and associated inflammation

Samuel E. Kennedy, sek2016@uga.edu, Rakesh Pathak, Shanta Dhar. Department of Chemistry, University of Georgia, Athens, Georgia 30609, United States

Prostate cancer is the most common cancer found in men in United States. In the late stages, metastasis and chemo-resistance induces tumor recurrence significantly affecting the morbidity and mortality of patients. Moreover, chronic inflammation associated with tumor tissues plays key roles in the metastasis of prostate cancer. In our continuing efforts to provide a therapeutic option for metastatic prostate cancer, we recently constructed a Pt(IV) prodrug, Platin-A, with the ability to release cisplatin, a widely used chemotherapeutic, and aspirin, an anti-inflammatory agent. However, clinical translation of small-molecule based therapeutics requires a suitable delivery system to achieve pharmacokinetics parameters and appropriate biodistribution. Activation of various proteins causes mitochondrial dysfunction, resulting in mitochondrial reactive oxygen species production and downstream signaling that promote inflammation-associated cancer. Using a mitochondria-targeted polymeric-nanoparticle as a delivery vehicle, we anticipated that Platin-A could be re-routed to the mitochondria of cancer cells and attack the mitochondrial DNA, thereby designing a targeted pathway for the well-established drug cisplatin. Platin-A exhibited anticancer and anti-inflammatory properties which were better than a combination of cisplatin and aspirin. This result highlights the advantages of blending an anti-inflammatory agent with a chemotherapeutic agent in a single prodrug. The enormous potential of Platin-A encouraged the design of additional Pt(IV) prodrugs to co-deliver cisplatin and aspirin. A promising design will be discussed here.

Reference:

Pathak, R. K.; Marrache, S.; Choi, J. H.; Berding, T. B. and Dhar, S . "The prodrug Platin-A: Simultaneous release of cisplatin and aspirin"
Angew. Chem. Int. Ed., 2014 , 53, 1963-1967.


Sunday, October 19, 2014 10:15 AM
Undergraduate Poster Session: Inorganic Chemistry II (10:15 AM - 11:45 AM)
Location: Sheraton Music City Hotel
Room: Plantation Ballroom

 

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