MultiTheranostics

Cancer is a leading cause of death and a major impediment to increasing life expectancy around the globe. Amongst all skin cancers, melanoma is a hard-to-treat disease, owing to its high potential for metastasis, and it remains as one of the most aggressive cancers. Single therapy is not efficient to tackle metastatic melanoma and a combination of therapies is thus emerging as a necessity to efficiently eradicate all cancer cells. Recently, immunotherapy, in particular immune checkpoint inhibitors (ICI), has become a powerful treatment strategy for cancer. Nevertheless, the physical barriers represented by cellular and non-cellular components of the tumour microenvironment combined with immune escape mechanisms of cancer, hamper an efficient tumour infiltration and patients’ responsiveness to ICI therapy. In this context, MultiTheranostic aims to develop theranostic nanoparticles for gene therapy-mediated immune checkpoint silencing and chemotherapy, exploiting the properties of magnetic nanoparticles to induce damage locally on the tumour microenvironment by magnetic hyperthermia (MH). This multimodal theranostic approach, incorporating MRI tracking, is versatile, as it could be also applied to other types of solid tumours. MultiTheranostic objectives are (i) to synthetize and validate a biocompatible magnetic lipid nanoparticle (NPs) incorporating silencing RNA against ICI targets, and chemotherapy (WP1,
WP2), (ii) to develop a tissue-engineered (TE) model for screening and monitoring the efficacy of the NPs (WP3), and (ii) to demonstrate the effectiveness of the final drug delivery system as a multimodal theranostic approach for metastatic melanoma (WP4). With MultiTheranostic the researcher will greatly expand her scientific expertise in the fields of nanotechnology and bioengineering, positioning her as a leading independent researcher, contributing to the advancement of nanomedicine in Europe and beyond.