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Abstract <p><b>Objective:</b> Quercetin, a flavonoid found in fruits and vegetables, is known for its antioxidant, anti-inflammatory, and cytotoxic properties. However, its poor water solubility limits its therapeutic potential. This study aimed to design and synthesize a nanocomposite for efficient quercetin delivery to DU-145 prostate carcinoma cells and evaluate its therapeutic effects. <b>Methods:</b> Ag<sub>2</sub>O@Quercetin nanoparticles (Ag<sub>2</sub>O@Quercetin NCs) were designed and synthesized to enhance the delivery of insoluble quercetin to DU-145 cells. The anti-tumor activities of the nanoparticles were evaluated using the MTT assay, Annexin V FITC/PI staining, scratch assay, and analysis of miR-34a and miR-181a expression patterns, along with their potential targets in cell migration and apoptosis <i>via</i> quantitative RT-PCR (Q-RT-PCR). <b>Results and Discussion:</b> Physicochemical characterization, including X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), differential thermal gravimetric (DTG) analysis, and FT-IR spectroscopy, confirmed the particle size, elemental composition, and thermal stability of the Ag<sub>2</sub>O@Quercetin NCs. The nanoparticles exhibited antiproliferative activity, with an IC<sub>50</sub> value of 55.27 µg/mL in DU-145 cells. The scratch assay demonstrated that Ag<sub>2</sub>O@Quercetin NCs inhibited cancer cell migration. Upregulation of miR-34a and downregulation of its potential targets, EGFR and TGF-β1, were observed in treated cells. Additionally, downregulation of oncomiR-181a and upregulation of their potential targets involved in apoptosis (<i>Casp8</i> and Casp9 genes) and anti-invasion (E-cadherin) were observed in treated cells. <b>Conclusions:</b> The results indicate that silver oxide nanoparticles are effective carriers for quercetin delivery to cancer cells. Ag<sub>2</sub>O@Quercetin NCs induce apoptotic pathways and inhibit cell migration and invasion in prostate cancer cells through the modulation of specific miRNAs and their associated targets.</p>

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Anti-Invasion and Apoptotic Induction Effects of Quercetin-Functionalized Silver Oxide (Ag2O) Nanoparticles on DU-145 Prostate Carcinoma Cells via Modulation of miR-34a, miR-181a, and Their Potential Targets

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • S. M. Mousavi Eshkelani,
  • A. Sejdeh Hassankiadeh,
  • M. Hajitabar,
  • Z. Shamsi Balasbaneh,
  • T. Kazemi,
  • H. Beheshti Dafchahi,
  • M. Shahriarinour,
  • M. Nikpassand,
  • N. Ranji,
  • R. S. Varma

摘要

Abstract

Objective: Quercetin, a flavonoid found in fruits and vegetables, is known for its antioxidant, anti-inflammatory, and cytotoxic properties. However, its poor water solubility limits its therapeutic potential. This study aimed to design and synthesize a nanocomposite for efficient quercetin delivery to DU-145 prostate carcinoma cells and evaluate its therapeutic effects. Methods: Ag2O@Quercetin nanoparticles (Ag2O@Quercetin NCs) were designed and synthesized to enhance the delivery of insoluble quercetin to DU-145 cells. The anti-tumor activities of the nanoparticles were evaluated using the MTT assay, Annexin V FITC/PI staining, scratch assay, and analysis of miR-34a and miR-181a expression patterns, along with their potential targets in cell migration and apoptosis via quantitative RT-PCR (Q-RT-PCR). Results and Discussion: Physicochemical characterization, including X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), differential thermal gravimetric (DTG) analysis, and FT-IR spectroscopy, confirmed the particle size, elemental composition, and thermal stability of the Ag2O@Quercetin NCs. The nanoparticles exhibited antiproliferative activity, with an IC50 value of 55.27 µg/mL in DU-145 cells. The scratch assay demonstrated that Ag2O@Quercetin NCs inhibited cancer cell migration. Upregulation of miR-34a and downregulation of its potential targets, EGFR and TGF-β1, were observed in treated cells. Additionally, downregulation of oncomiR-181a and upregulation of their potential targets involved in apoptosis (Casp8 and Casp9 genes) and anti-invasion (E-cadherin) were observed in treated cells. Conclusions: The results indicate that silver oxide nanoparticles are effective carriers for quercetin delivery to cancer cells. Ag2O@Quercetin NCs induce apoptotic pathways and inhibit cell migration and invasion in prostate cancer cells through the modulation of specific miRNAs and their associated targets.