Sonodynamic Treatment Induces Selective Killing of Cancer Cells in an In Vitro Co-Culture Model.

Federica Foglietta,Francesca Giuntini,Nadia Barbero,Gianni Durando,Enzo Terreno,Patrizia Panzanelli,Vanessa Pinnelli,Roberto Canaparo,Loredana Serpe

doi:10.3390/cancers13153852

Abstract

Simple SummaryA review of over six decades of cancer chemotherapies, including recent immunotherapy, reveals partial success in the battle against cancer. One of the main reasons for this slow progress is the failure, by mainstream anticancer treatments, to distinguish between cancer cells and normal cells. For this reason, the aim of our study was to assess if sonodynamic therapy (SDT), a new anticancer approach, can affect cancer cells only, avoiding any harmful effects on normal cells. SDT aims to cure malignant tumors by using a chemical compound (sonosensitizer) triggered by ultrasound exposure. For this purpose, the effects on cancer cells and normal cells, namely HT-29 cells and HDF 106-05 cells, subjected to sonodynamic treatment were investigated. Our results show that, according to different plasma membrane properties of cancer cells and normal cells, a different sonodynamic effect occurs, reaching a remarkable cytotoxic effect on cancer cells only.Sonodynamic Therapy (SDT) is a new anticancer strategy based on ultrasound (US) technique and is derived from photodynamic therapy (PDT); SDT is still, however, far from clinical application. In order to move this therapy forward from bench to bedside, investigations have been focused on treatment selectivity between cancer cells and normal cells. As a result, the effects of the porphyrin activation by SDT on cancer (HT-29) and normal (HDF 106-05) cells were studied in a co-culture evaluating cell cytotoxicity, reactive oxygen species (ROS) production, mitochondrial function and plasma membrane fluidity according to the bilayer sonophore (BLS) theory. While PDT induced similar effects on both HT-29 and HDF 106-05 cells in co-culture, SDT elicited significant cytotoxicity, ROS production and mitochondrial impairment on HT-29 cells only, whereas HDF 106-05 cells were unaffected. Notably, HT-29 and HDF 106-05 showed different cell membrane fluidity during US exposure. In conclusion, our data demonstrate a marked difference between cancer cells and normal cells in co-culture in term of responsiveness to SDT, suggesting that this different behavior can be ascribed to diversity in plasma membrane properties, such as membrane fluidity, according to the BLS theory.

Highlights

Cancer is a major public health problem worldwide and continuous scientific efforts in this field are clearly needed [1]
Since it has been reported that in cancer cells, mitochondria are mostly localized at a perinuclear level, whereas in normal cells, they are spread all over the cellular body [35,36], and it has been considered that porphyrins accumulate preferentially in mitochondria [37], we suggested that the palladium (II) porphyrin complex (Pd-P) complex preferentially accumulated in the mitochondria in both cell lines
Our findings suggested that, in Sonodynamic Therapy (SDT), the US-mediated intracellular sensitizer activation could be more influenced by differences in the cell structure of HT-29 and HDF 106-05 cells compared to photodynamic therapy (PDT) because, due to the type of energy released from the light, the selectivity of photodynamic action can be better achieved investigating cell organelles-targeted photosensitizers instead of cell structure differences between normal and cancer cells [42]

Summary

Introduction

Cancer is a major public health problem worldwide and continuous scientific efforts in this field are clearly needed [1]. In recent decades, thanks mainly to increasing knowledge on cancer molecular biology and growing interest in applying bioand nano-technology techniques against this pathology, cancer therapeutic strategies have notably changed [2,3] Despite these advancements, the overall cancer death rate still remains high as the critical issue of targeting cancer cells with high selectivity has not been reached for most cancers [4]. The aim of our work was to shed new light on the SDT mechanism of action and to understand if selectivity towards cancer could be one of the main features of this approach To this end, in our previous investigations, different outcomes of cancer cells and normal cells to SDT were reported, supporting the finding that cancer cells and normal cells behave differently in response to SDT [12]. Geltmeier and colleagues reported that a tension/compression force of US can provoke damage preferentially on cancer cells, compared to normal cells [14]

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