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.

中文翻译：

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氧化铁纳米颗粒：通过 H2AX 磷酸化诱导 DNA 损伤并通过 ERK 去磷酸化阻碍增殖，选择性地靶向体外黑色素瘤细胞

本研究探讨了氧化铁磁性纳米颗粒 (mNP) 的独特特性及其在癌症治疗中的潜在应用，重点关注黑色素瘤。三种类型的 mNP 均经过安全性预先验证，并进行了分子分析，以揭示黑色素瘤细胞中激活的信号通路。利用蛋白质印迹技术，研究表明 mNP 会诱导细胞毒性，通过 ERK1/2 去磷酸化阻碍增殖，并促进促凋亡作用，包括通过诱导 H2AX 磷酸化来损伤 DNA。此外，体外磁热疗显着增强了黑色素瘤细胞的细胞损伤。此外，通过电感耦合等离子体质谱 (ICP-MS) 分析对细胞内铁水平进行定量，揭示了有效诱导细胞损伤所需的精确剂量。这些令人信服的发现不仅揭示了 mNP 在黑色素瘤治疗中的治疗潜力，而且为未来的研究开辟了令人兴奋的途径，预示着开发靶向有效癌症疗法的新时代。事实上，通过辨别有效剂量，我们的方法有助于优化氧化铁磁性纳米颗粒的治疗利用，从而能够诱导精确靶向和控制的细胞反应。