Dipartimento di Scienza e Tecnologia del Farmaco

Descrizione del progetto

Members of other units:
Greta Varchi, Marco Ballestri. Pierluigi Civera, Andrea Francovick. Enrico Davoli, Giancarlo Bianchi, Massimo Broggini, Luigi Cappellini

Partners:
Department of Electronics and Telecommunications (DET), Politecnico of Turin, Italy 
Consiglio Nazionale delle Ricerche, Institute of Organic Synthesis and Photoreactivity (ISOF), Bologna, Italy 
Mario Negri - Institute for Pharmacological Research, Milano, Italy
New Center of Exellence in Preclinical Imaging, Bioindustry Park, University of Turin, Colleretto Giacosa (Turin), Italy

Sponsors:
Associazione Italiana per la  Ricerca sul Cancro: MFAG13048

Description
Sonodynamic therapy (SDT), which refers to the synergistic effect of chemical compounds (sonosensitizers) and ultrasound, is a promising new modality for cancer treatment. This followed the assumption that inertial cavitation ultrasound may cause an energy transfer which is able to cause electronic excitation in the sonosensitizer resulting in the generation of a variety of free radicals. However, no clinical data have been published on the subject, yet. This may be because of the lack of strong evidence of the SDT safety and efficacy in in vivo studies.

Our preliminary in vitro and in vivo studies on the synergistic effect of a combination of high energy shock wave (HESW) and common sonosensitizers, such as 5-aminolevulinic acid, have shown encouraging results. Deeper investigation is needed to clarify the effects of HESW on cancer tissues and to address some important issues such as efficacy and safety. First of all, the safety of this new anti-cancer approach will be studied. It is known that physical manipulation may accelerate the metastatic spread of tumor cells. Therefore, to address this issue, an experimental model of pulmonary metastasis will be carried out to assess the effects of SDT with HESW.

Turning to efficacy, nowadays, the sonodynamic effect is promoted using molecules which have both photo- and sonosensitizer properties. Unfortunately, this kind of molecule is less active when used as a sonosensitizer than when involved in photodynamic therapy. Therefore to address this issue we will direct our efforts to elucidate the relationship between chemical structure and sonodynamic effect and to increase the sonosensitizer concentration into the target site. The efficacy will be investigated on in vitro multicellular tumor spheroids and in vivo orthotopic syngeneic breast and cancer models in order to clarify the synergistic effect between new sonosensitizers and HESW.

To sum up, we would like to deeply investigate the efficacy and safety of this anti-cancer approach using innovative technologies such as novel sonosensitizer systems, matrix-assisted laser desorption/ionization time-offlight (MALDI-TOF) analysis and experimental models for quantitative metastasis study.

Keywords:
Sonodynamic Therapy, High Energy Shock Waves, Ultrasound, Acoustic Cavitation, Sonosensitizers, Nanosonosensitizers, Cancer

Links:
Politecnico of Turin