Dataset Information

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.

SUBMITTER: Milan Rois P

PROVIDER: S-EPMC6352695 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Milán Rois Paula P Latorre Alfonso A Rodriguez Diaz Ciro C Del Moral Álvaro Á Somoza Álvaro Á

Biomimetics (Basel, Switzerland) 20180925 4

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 microRN ...[more]

PMID: 31105250

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Project description:Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT.

Dataset Information

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

Publications

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

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