Despite recent advances in the understanding of fundamental cancer biology, cancer remains the second most common cause of death in the United States. One of the primary factors indicative of high cancer morbidity and mortality and aggressive cancer phenotypes is tumors with a low extracellular pH (pHe). Thus, the ability to measure tumor pHe in vivo using non-invasive and accurate techniques that also provide high spatiotemporal resolution has become increasingly important and is of great interest to researchers and clinicians. Recently, the use of pH-responsive polymer systems in cancer diagnostics and treatment has received considerable attention due to their ability to undergo conformational changes in response to changes in the environmental pH. For example, pH-responsive drug delivery systems have been developed where the drug is encapsulated in a micelle structure when circulating in the blood stream and is selectively released via a hydrophobic to hydrophilic transition once it arrives at the tumor site. We have developed pH-responsive nanoscale multimodal contrast agents for magnetic resonance imaging (MRI) that demonstrate large changes in relaxivity to improve both the selectivity and sensitivity of in vivo pHe measurement. A series of pH-responsive biocompatible block polymers with pKa's ranging from 5.0 to 7.5 have been synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. These copolymers have then been used to modify gadolinium nanoparticles to design a smart contrast agent for MRI, which will potentially allow for enhanced diagnostics in the treatment of cancer. Scheme of Proposed 'Smart' MRI Contrast Agents

Synthesis of tertiary amine-based pH-responsive block copolymers for use as "smart" MRI contrast agents

247th National Meeting (2014)

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