Synergistic Cisplatin-induced cell death by ultrasound-microbubble mediated intracellular delivery in breast cancer cells

Ultrasound-microbubble (USMB) potentiated cisplatin (CDDP) therapy was assessed in human breast cancer cells. Cells, MDA-MB-231, in suspension were exposed to USMB and CDDP at varying conditions, during which microbubble cavitation activity was measured using passive cavitation detection and 48 hours post-treatment cell viability and intracellular platinum concentration were measured using MTT assay and mass cytometry, respectively. USMB synergistically enhanced cell death (~20 fold) when combined with CDDP and significantly increased intracellular CDDP concentration (~8 fold) compared to CDDP treatment alone. Cell death and intracellular CDDP concentration were correlated to microbubble cavitation activity, which increased with peak negative pressure and microbubble concentration. Combined treatment of USMB and CDDP at relatively lower integrated cavitation dose (ICD) induced a synergistic effect on cell death whereas ICD greater than 10 induced an additive effect. USMB mediated CDDP intracellular accumulation synergistically enhances cell death in CDDPresistant breast cancer cells.