Ultrasound and Microbubbles Combined with Gold Nanoparticles Enhanced the Therapeutic Effect of Radiotherapy in Breast Cancer Cells

Gold nanoparticles have been shown to enhance local radiation dose due to its high Z value.  Ultrasonically-stimulated microbubbles at therapeutic conditions can sensitize cells to ionizing radiation and enhance cell permeability allowing gold nanoparticles to cross the plasma membrane.  In this study, ultrasound-microbubble potentiated enhancement of cell death in combination with gold nanoparticles and ionizing radiation is investigated in vitro.  A suspension model of breast cancer (MDA-MB-231) cells was exposed to ultrasound and microbubbles (USMB), gold nanoparticles (AuNP) and ionizing radiation (XRT).  A 12 nm spherical AuNPs at concentrations of 7.8 x10¹⁰ nps/mL and 1.6 x 10¹¹ nps/mL were investigated at fixed USMB conditions of 500 kHz pulse center frequency, 580 kPa peak negative pressure, 10 μs pulse duration, 60s insonation time, Definity® microbubbles at 3.3% (v/v) and XRT dose of 2 Gy.  Cell viability post treatment was evaluated using clonogenic assay.  The application of AuNP and USMB induced a synergistic increase in cell death when combined with XRT.  A 22 fold increase in cell death was observed with the combined treatment (AuNP+USMB+XRT=3±0.4%) compared to radiotherapy only (XRT=65±3%).  The combined treatment of ultrasound-microbubbles with gold nanoparticles followed by radiotherapy induced a synergistic effect in cell death.