Microbubble-enhanced ultrasound liberation of mRNA biomarkers in vitro

Blood-borne biomarkers have great potential in diagnostic medicine, but low concentrations, inability to determine their source and lack of a patient baseline have limited their success in both research and clinical medicine. D'Souza et al. previously demonstrated that ultrasound-induced sonoporation can be used to liberate protein biomarkers from a colorectal cancer into the surrounding serum, overcoming many of the limitations of blood-borne biomarkers. In this study we build on D'Souza's work, extending this technique to nucleic acids, specifically mammaglobin mRNA-a potential diagnostic biomarker for breast cancer metastases. Furthermore, we propose to use ultrasound contrast agents, lipid-stabilized microbubbles, to enhance the effects of sonoporation and further amplify the biomarker levels. We demonstrate that microbubbles can enhance mammaglobin mRNA levels by two to three orders of magnitude greater than background levels and one to two orders of magnitude greater than ultrasound alone.