Sonodynamic therapy (SDT) represents an emerging approach that offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. It involves the sensitization of target tissues with a non-toxic sensitizing chemical agent and subsequent exposure of the sensitized tissues to relatively low-intensity ultrasound. Essentially, both aspects (the sensitization and ultrasound exposure) are harmless, and cytotoxic events occur when both are combined. Due to the significant depth that ultrasound penetrates tissue, the approach provides an advantage over similar alternative approaches, such as photodynamic therapy (PDT), in which less penetrating light is employed to provide the cytotoxic effect in sensitized tissues. This suggests that sonodynamic therapy may find wider clinical application, particularly for the non-invasive treatment of less accessible lesions. Early SDT-based approaches employed many of the sensitizers used in PDT, although the manner in which ultrasound activates the sensitizer differs from activation events in PDT. Here we will review the currently accepted mechanisms by which ultrasound activates sensitizers to elicit cytotoxic effects. In addition, we will explore the breath of evidence from in-vitro and in-vivo SDT-based studies, providing the reader with an insight into the therapeutic potential offered by SDT in the treatment of cancer.

A new class of iodinated cyanine dyes have been prepared for use in NIR excited photodynamic therapy (PDT) and demonstrated improved efficacy in two pancreatic cell lines as well as excellent tumour control in a murine model of the disease.

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Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (OMB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to OMBs (OMB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the OMB-Gem and a Rose Bengal loaded OMB (OMB-RB) as a targeted treatment for pancreatic cancer. Specifically, UTMD using the OMB-Gem and OMB-RB conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299 pancreatic cancer cells by >60% (p < 0.001) and provided significant tumour growth delay (>80%, p < 0.001) compared to untreated animals when human xenograft MIA PaCa-2 tumours were treated in SCID mice. The toxicity of the OMB-Gem conjugate was also determined in healthy non-tumour bearing MF1 mice and revealed no evidence of renal or hepatic damage. Therefore, the results presented in this manuscript suggest that chemo-sonodynamic therapy using the OMB-Gem and OMB-RB conjugates, is potentially an effective targeted and safe treatment modality for pancreatic cancer.