Fighting cancer relapse with ultrasound activated nanoparticles: preliminary studies of possible extracorporeal circulation set-ups

Nowadays, recurrence of the primary tumor affects a relatively high number of patients, because of the not complete remission of the tumor by the treatment: the minimal residual disease (MRD) continues its activity, initiating relapse and metastasis. Thus, further treatments must be introduced, causing additional health issues on patients and requiring much higher costs. Cancer’s progression, recurrence and metastasis mostly occurs by means of circulating tumor cells (CTCs): they belong to the primary tumor and become able to leave it and diffuse through the bloodstream, forming new tumors (metastases) in distant tissues and organs. The XtraUS project, whose initial steps are represented by this Master Thesis, aims to prevent cancer relapse and metastasis by developing a breakthrough technology against CTCs: the novel idea introduced by this technology is an extracorporeal set – up (cartridge) along which blood circulates, where an innovative stimuli-responsive, targeted and non-immunogenic nanoconstruct is injected and activated by ultrasounds (US) to act against flowing CTCs in the blood. To achieve this goal, the extracorporeal cartridge, the US application and the nanoconstruct must be properly designed, in order to exploit their synergistic action in terms of therapeutic and cytotoxic effects on CTCs. In particular, the mechanism of action of the US – activated nanoconstructs has been experimentally studied in the work of this Thesis. Furthermore, many preliminary cartridges and US settings have been tested in water – based solutions, with the goal of maximize the US effect on the nanoconstruct. To perform such measurements, two state-of-the-art methods have been used, such as sonochemiluminescence (SCL) and Electron Paramagnetic Resonance (EPR) spectroscopy, combined with mathematicl simulations. In parallel, numerical simulations of the US field behaviour in various set – up have been performed. They have allowed to observe the resulting pressure and intensity spatial distributions, thank to which it is possible to have a clear idea about how designing future extracorporeal cartridges for this application. The obtained results and the many different conditions tested have demonstrated the best preliminary set – up in terms US-activated constructs and materials to be used to build the extracorporeal circulation set up. These results set the basis for a strong theoretical and experimetal approach to evaluate the effect of US in water based system with nanostrucutres and open the way for future studies and measurements with living cancer cells.