Optimization of Phase-Change Contrast Agents for Targeting MDA-MB-231 Breast Cancer Cells

Abstract

<p class="first" id="P1">Breast cancer remains a leading cause of death for women throughout the world. Recent advances in medical imaging technologies and tumor targeting agents signify vast potential for progress toward improved management of this global problem. Phase-change contrast agents (PCCAs) are a dynamic imaging agent with practical applications in both the research and clinical settings. PCCAs possess characteristics that allow for cellular uptake where they can be converted from liquid phase PCCAs to gaseous microbubbles via ultrasound energy. Previously, we reported successful internalization of folate-targeted PCCAs in MDA-MB-231 breast cancer cells followed by ultrasound-mediated activation to produce internalized microbubbles. This study examines the binding, internalization, and activation of folate-receptor targeted PCCAs within MDA-MB-231 breast cancer cells as a function of gaseous core compositions, incubation time, and ultrasound exposure period. <i>In vitro</i> results indicate that internalization and ultrasound-mediated activation of PCCAs was significantly greater using a 50:50 mixture of decafluorobutane: dodecafluoropentane compared to other core compositions- 50:50 octafluoropropane: decafluorobutane (p &lt;0.0001), decafluorobutane (p &lt;0.04) and dodecafluoropentane (p &lt;0.0001). Furthermore, it was shown that PCCAs composed of perfluorocarbons with higher boiling points responded with greater activation efficiency when exposed to 12 seconds of ultrasound exposure as opposed to 4 seconds of ultrasound exposure. When evaluating different incubation times, it was found that incubating the PCCAs with breast cancer cells for 60 minutes did not produce significantly greater internalization and activation compared to 10 minutes; this was concluded from comparing the number of microbubbles present per cell prior to ultrasound versus post-ultrasound, and finding a ratio of intracellular MB Post-US/Pre-US, 3.46 vs. 3.14, respectively. The data collected in this study helps demonstrate further optimization of folate-receptor targeted PCCAs for breast cancer targeting and imaging. </p>