Enhancing laser thermal-therapy using ultrasound–microbubbles and gold nanorods of in vitro cells

Abstract

Gold nanorods (GNRs) are being exploited for their absorption properties to improve thermal therapy. However, a key challenge is delivering sufficient concentration of GNRs to induce a therapeutic effect. In this study, ultrasound and microbubbles (USMBs) were used to enhance intracellular uptake of GNRs. AML-5 cells in suspension (0.6mL) were exposed to ultrasound (1.3 and 1.7MPa peak negative pressure) and definity microbubbles (1.7% v/v) for 1min at varying GNR concentrations (0–2.5×1011 per mL). Following ultrasound–microbubble treatment, cells were centrifuged twice and treated with an 810nm laser at an average fluence rate of 3.6W/cm2 for 5min. In addition, cells were incubated with GNRs for 12h prior to laser treatment. Following the treatment, cell viability (VPI) was assessed using propidium iodide (PI) and flow cytometry. Cell viability decreased by ∼4-folds with the combined treatment of USMB+GNR+Laser (VPI=17%) compared to cells incubated with GNR+Laser (VPI=68%). This effect depended on ultrasound pressure and GNR concentration. Higher cell death was achieved at higher GNR concentration and 1.3MPa peak negative pressure. Cell viability decreased from 92% to 29% with increasing GNR concentration from 1×1011 to 1.5×1011GNR/mL. In addition, higher temperatures were observed using a thermal camera with the combined treatment (USMB+GNR+Laser) of 59±1°C compared to 54±0.9°C for cells incubated with GNRs. The combined treatment of ultrasound–microbubble and gold nanorod laser induced thermal-therapy improved treatment response of in vitro cells.