Integration of Transcriptomics and Metabolomics to Reveal the Molecular Mechanisms Underlying Rhodium Nanoparticles-Based Photodynamic Cancer Therapy.

Andres Machuca,Daniela S Anunciação,Estefania Garcia-Calvo,Jose L Luque-Garcia

doi:10.3390/pharmaceutics13101629

Andres Machuca, Daniela S Anunciação + Show 2 more

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https://doi.org/10.3390/pharmaceutics13101629

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Abstract

Rhodium nanoparticles have recently been described as promising photosensitizers due to their low toxicity in the absence of near-infrared irradiation, but their high cytotoxicity when irradiated. Irradiation is usually carried out with a laser source, which allows the treatment to be localized in a specific area, thus avoiding undesirable side effects on healthy tissues. In this study, a multi-omics approach based on the combination of microarray-based transcriptomics and mass spectrometry-based untargeted and targeted metabolomics has provided a global picture of the molecular mechanisms underlying the anti-tumoral effect of rhodium nanoparticle-based photodynamic therapy. The results have shown the ability of these nanoparticles to promote apoptosis by suppressing or promoting anti- and pro-apoptotic factors, respectively, and by affecting the energy machinery of tumor cells, mainly blocking the β-oxidation, which is reflected in the accumulation of free fatty acids and in the decrease in ATP, ADP and NAD+ levels.

Highlights

The use of nanomaterials in cancer treatment has attracted much interest over recent years because of the wide range of possibilities that these materials can offer due to their unique properties such as their reduced size, improved physico-chemical properties and ease of surface modifications, which have shown great potential for biomedical applications [1,2,3,4]
Photodynamic performance of rhodium nanoparticles (RhNPs) was confirmed by the decrease in absorbance Photodynamic performance of RhNPs was confirmed by the decrease in absorbance of DPBF after NIR exposure of an aqueous RhNPs suspension (Figure 1)
A multi-omics approach based on the integration of transcriptomics and metabolomics has enabled a deep characterization of the molecular mechanisms involved in the potential of RhNPs used in combination with NIR irradiation for photodynamic therapy against cancer

Summary

Introduction

The use of nanomaterials in cancer treatment has attracted much interest over recent years because of the wide range of possibilities that these materials can offer due to their unique properties such as their reduced size, improved physico-chemical properties and ease of surface modifications, which have shown great potential for biomedical applications [1,2,3,4]. An interesting characteristic of some metal nanoparticles is their highly tunable interaction properties with external electromagnetic radiation, which is potentially useful in photodynamic therapy (PDT). PDT exploits the interaction between the nanomaterial and the electromagnetic radiation to induce cell damage and prevent tumor growth [9]. Because the irradiation can be performed in a perfectly confined area, where the tumor is located, the use of metallic nanoparticles as photosensitizing agents in PDT constitutes a highly selective approach to tumor treatment, minimizing side effects on healthy cells [10,11]. Among the different types of nanoparticles that have been proposed as photosensitizing agents for PDT, the use of rhodium nanoparticles (RhNPs) is promising due to their low toxicity over a wide range of concentrations when near-infrared (NIR) irradiation is not applied [12]. Despite the good results obtained, it is necessary to further investigate the molecular mechanisms responsible for the observed anti-tumoral effect, as a prior step to their evaluation in pre-clinical models

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