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Leveraging Aberrant Iron Metabolism as a Method for Selective Drug Delivery and Imaging In Vivo

  • Author(s): Muir, Ryan Keith
  • Advisor(s): Renslo, Adam R
  • et al.
Abstract

Iron is a nutrient essential for cell growth and proliferation, however too high of a concentration can cause the formation of toxic reactive oxygen species. As a result, normal cells tightly regulate iron metabolism. Many cancers have been noted to possess aberrant expression of various proteins in the iron metabolism pathway, with a strong correlation between a higher avidity for iron and worse patient prognosis. Recently the Renslo lab has sought to leverage this elevated level of iron utilizing an Fe(II)-activated prodrug platform based on the reactivity of 1,2,4-trioxolanes (TRX). Previous studies have demonstrated selective delivery of amine-bearing cytotoxins to cancers with elevated Fe(II) pools. Here we report expanding this work in three ways: 1. Design of a therapeutic diagnostic PET probe to identify potential suitable cancers for this TRX-based approach. 2. Delivery of targeted anticancer therapeutics in order to gain an additional level of selectivity. 3. Expanding the TRX scaffold to accommodate hydroxamate-containing chemotherapeutics.

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