Iron Oxide Nanoparticles: Selectively Targeting Melanoma Cells In Vitro by Inducing DNA Damage via H2AX Phosphorylation and Hindering Proliferation through ERK Dephosphorylation

Author:

Prokopiou Danai E.12,Chillà Anastasia3ORCID,Margheri Francesca3,Fibbi Gabriella3,Laurenzana Laurenzana3ORCID,Efthimiadou Eleni12ORCID

Affiliation:

1. Inorganic Chemistry Laboratory, Chemistry Department, National and Kapodistrian University of Athens, Panepistimiopolis, 157 71 Zografou, Greece

2. Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, 153 41 Athens, Greece

3. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale G.B. Morgagni, 50, 50134 Florence, Italy

Abstract

This study investigates the distinctive characteristics of iron oxide magnetic nanoparticles (mNPs) and their potential application in cancer therapy, focusing on melanoma. Three types of mNPs, pre-validated for safety, underwent molecular analysis to uncover the activated signaling pathways in melanoma cells. Using the Western blot technique, the study revealed that mNPs induce cytotoxicity, hinder proliferation through ERK1/2 dephosphorylation, and prompt proapoptotic effects, including DNA damage by inducing H2AX phosphorylation. Additionally, in vitro magnetic hyperthermia notably enhanced cellular damage in melanoma cells. Moreover, the quantification of intracellular iron levels through Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis unveils the precise dosage required to induce cellular damage effectively. These compelling findings not only shed light on the therapeutic potential of mNPs in melanoma treatment but also open exciting avenues for future research, heralding a new era in the development of targeted and effective cancer therapies. Indeed, by discerning the effective dose, our approach becomes instrumental in optimizing the therapeutic utilization of iron oxide magnetic nanoparticles, enabling the induction of precisely targeted and controlled cellular responses.

Funder

Greece and the European Union

Associazione Italiana Ricercasul Cancro

Tuscany Region

Publisher

MDPI AG

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