No abstract

Controlled delivery of multiple chemotherapeutics can improve the effectiveness of treatments and reduce side effects and relapses. Here in, we used albumin-stabilized gold nanoclusters modified with doxorubicin and SN38 (AuNCs-DS) as combined therapy for cancer. The chemotherapeutics are conjugated to the nanostructures using linkers that release them when exposed to different internal stimuli (Glutathione and pH). This system has shown potent antitumor activity against breast and pancreatic cancer cells. Our studies indicate that the antineoplastic activity observed may be related to the reinforced DNA damage generated by the combination of the drugs. Moreover, this system presented antineoplastic activity against mammospheres, a culturing model for cancer stem cells, leading to an efficient reduction of the number of oncospheres and their size. In summary, the nanostructures reported here are promising carriers for combination therapy against cancer and particularly to cancer stem cells.

No 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.