Intracellular Fate of Sub-Toxic Concentration of Functionalized Selenium Nanoparticles in Aggressive Prostate Cancer Cells

Author:

Bissardon Caroline1ORCID,Proux Olivier2ORCID,Gazze Salvatore Andrea3,Filhol Odile4ORCID,Toubhans Benoît3,Sauzéat Lucie5ORCID,Bouchet Sylvain5,Lewis Aled R.3,Maffeis Thierry3ORCID,Hazemann Jean-Louis6ORCID,Bayat Sam1ORCID,Cloetens Peter7,Conlan R. Steven3ORCID,Charlet Laurent8,Bohic Sylvain17ORCID

Affiliation:

1. Université Grenoble Alpes, Inserm, UA7, Synchrotron Radiation for Biomedicine (STROBE), 38400 Grenoble, France

2. OSUG, UAR 832 CNRS, Université Grenoble Alpes, IRD, INRAe, Météo-France, 38041 Grenoble, France

3. Swansea University Medical School, Swansea University, Swansea SA2 8PP, UK

4. Laboratoire de Biologie et Biotechnologies pour la Santé, IRIG-DS, Inserm U1292, CEA, Université Grenoble-Alpes, 38054 Grenoble, France

5. Institute of Biogeochemistry and Pollutant Dynamics, ETH Zurich, CH-8092 Zurich, Switzerland

6. Institut Néel CNRS-UGA, 25 Avenue des Martyrs, 38042 Grenoble, France

7. ESRF—The European Synchrotron Radiation Facility, 38043 Grenoble, France

8. ISTerre, Université Grenoble Alpes, 38041 Grenoble, France

Abstract

Selenium 0 (Se0) is a powerful anti-proliferative agent in cancer research. We investigated the impact of sub-toxic concentrations of Se0 functionalized nanoparticles (SeNPs) on prostate cancer PC-3 cells and determined their intracellular localization and fate. An in-depth characterization of functionalized selenium nanoparticles composition is proposed to certify that no chemical bias relative to synthesis issues might have impacted the study. Selenium is an extremely diluted element in the biological environment and therefore requires high-performance techniques with a very low detection limit and high spatial resolution for intracellular imaging. This was explored with state-of-the-art techniques, but also with cryopreparation to preserve the chemical and structural integrity of the cells for spatially resolved and speciation techniques. Monodisperse solutions of SeNPs capped with bovine serum albumin (BSA) were shown to slow down the migration capacity of aggressive prostate cancer cells compared to polydisperse solutions of SeNPs capped with chitosan. BSA coating could prevent interactions between the reactive surface of the nanoparticles and the plasma membrane, mitigating the generation of reactive oxygen species. The intracellular localization showed interaction with mitochondria and also a localization in the lysosome-related organelle. The SeNPs-BSA localization in mitochondria constitute a possible explanation for our result showing a very significant dampening of the PC-3 cell proliferation capabilities. The purpose of the use of sublethal compound concentrations was to limit adverse effects resulting from high cell death to best evaluate some cellular changes and the fate of these SeNPs on PC-3. Our findings provide new insight to further study the various mechanisms of cytotoxicity of SeNPs.

Funder

INCA

Publisher

MDPI AG

Subject

General Materials Science,General Chemical Engineering

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