Development of saporin-based therapeutic options for the treatment of solid tumors.

Up to now, cancer represents one of the most challenging disease to treat, mostly due to its ability to adapt and negatively respond to current available therapies. Over the past 30 years, Ribosome Inactivating Proteins (RIPs) have attracted great interest in the scientific community for their therapeutic potential. Indeed, such toxins have been extensively used as potent and versatile therapeutic weapons due to important advantages compared to chemotherapeutics: for instance, they act independently form cell cycle, killing both quiescent and dividing cells, limiting the development of cancer resistance. However, the successful application of toxins-based therapeutics to solid tumors remains to be demonstrated. In this study, we explored the potential use of the plant-RIP saporin (SAP) for the treatment of solid tumors. In particular, we propose two different strategies, in which SAP is selectively and safely conveyed to malignant cells either in the form of recombinant protein through genetically fused targeting moieties, or throughout cell-derived extracellular vesicles as vehicles. Overall our data indicate that SAP-based recombinant proteins are promising antitumoral therapeutic options. Applied as single or combined treatment, as well as used together with traditional therapeutics, they appropriately address both intra and inter- tumor heterogeneity. In addition, the use of exosomes as SAP nanocarriers is a promising strategy to improve safety and drug delivery to tumor cells.