Reprogramming Cells for Synergistic Combination Therapy with Nanotherapeutics against Uveal Melanoma.

ABSTRACT

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and around half of the patients develop metastasis and die shortly after because of the lack of effective therapies for metastatic UM. Consequently, new therapeutic approaches to this disease are welcome. In this regard, microRNAs have been shown to have a key role in neoplasia progression and have the potential to be used as therapeutic tools. In addition, in different cancers including UM, a particular microRNA signature appears that is different from healthy cells. Thus, restoring the regular levels of microRNAs could restore the normal behavior of cells. In this study, four microRNAs downregulated in UM have been chosen to reprogram cancer cells, to promote cell death or increase their sensitivity to the chemotherapeutic SN38. Furthermore, to improve the internalization, stability and/or solubility of the therapeutic molecules employed in this approach, gold nanoparticles (AuNPs) were used as carriers. Remarkably, this study found a synergistic effect when the four oligonucleotides were employed and when the chemotherapeutic drug was added.