Despite significant advances in cancer treatment over the past five decades, survival outcomes for pancreatic cancer have remained largely unchanged. The effectiveness of chemotherapy as a treatment for pancreatic cancer is limited by the dense, protective tumour stroma, which impedes drug delivery. Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising strategy for enhancing the delivery of chemotherapy agents to solid tumours. In this study, we report the development and evaluation of a novel microbubble (MB) formulation, ST-001, which incorporates paclitaxel chemotherapy and a Rose Bengal sonosensitiser for targeted chemo-sonodynamic therapy of pancreatic cancer. The principle of UTMD using ST-001 was demonstrated in a murine model of pancreatic cancer, where B-mode ultrasound imaging was used to visualize MB accumulation within the tumour and its subsequent clearance following the application of therapeutic ultrasound. Preclinical efficacy studies demonstrated a significant survival advantage in ST-001 treated mice, which survived more than twice as long as those treated with standard Taxol, despite receiving only 14% of the paclitaxel dose. Additionally, a preclinical toxicology study in healthy mice demonstrated an excellent safety profile for ST-001, with no adverse effects observed in key hematological and blood biochemical markers, or in the histology of the spleen, liver, and kidneys.