Combination of Gemcitabine with regulated inertial and stable cavitation on a 3-D <i>in vitro</i> pancreatic tumor model

The prognosis of pancreatic cancer is poor because of resistance to current treatments due to its dense tumoral microenvironment. Cavitation has been proposed to favor the penetration of chemotherapies. In this work, both inertial and stable cavitations were applied to 3-D in vitro pancreatic tumor cell model in combination with Gemcitabine. Inertial cavitation aimed at softening the dense fibrous tumors while stable cavitation is aimed at enhancing drug diffusion. Conditions for regulated inertial cavitations are generated with transducers operating at 1.1 MHz, variable PNP up to 7MPa, 5% DC and 250 Hz PRF. The activity of inertial cavitation was quantified acoustically using a cavitation index (CI) calculated from the average acoustic amplitude of inharmonics frequency bands between 2.475 and 5.775 MHz recorded with a PCD. Chemical dosimetry of cavitation activity was assessed using terephthalic acid by measuring the induced fluorescence. Experiments were performed using two different but geometrically similar systems for which the sensitivity of the PCD was measured. Both systems generated similar cavitation activity when using the CI expressed in Pa. This method of quantifying inertial cavitation may provide a useful metric of comparison between systems in order to allow for direct comparison of experimental conditions.