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Background <p>Glioblastoma (GBM), the most aggressive primary brain tumor, faces significant treatment challenges due to drug resistance, blood–brain barrier limitations, and severe side effects of conventional therapies. This study aimed to develop and evaluate a nanotechnology-based therapeutic approach using selenium-loaded β-cyclodextrin-combretastatin A-4 nanoparticles (Se(B-CD-CA-4-NPs)) to overcome these limitations and enhance treatment efficacy.</p> Methods <p>The Se(B-CD-CA-4-NPs) complex was synthesized and characterized for morphology, size, stability, and selenium loading capacity. In vitro studies included MTT assay, cell apoptosis, scratch assay, gelatin zymography, and qPCR were used to assess the effect of the newly synthesized complex on U-87MG glioblastoma cell viability, cell death, migration, MMP-2 and MMP-9 activity, and mRNA expression level of apoptosis-related genes.</p> Results <p>The nanoparticles exhibited a spherical morphology (25.78 ± 3.4&#xa0;nm), negative surface charge, and high stability. The IC<sub>50</sub> of the synthesized complex was 1.629&#xa0;μM in U-87MG cancer cells. The Se(B-CD-CA-4-NPs) complex significantly reduced U-87MG cell viability, migration and invasion. Additionally, the complex induced cell apoptosis via upregulation of the <i>BAX</i>/<i>BCL-2</i> ratio in cancer cells. Moreover, the Se(B-CD-CA-4-NPs) complex inhibited metastasis by suppressing the activity and expression of MMP-2 and MMP-9.</p> Conclusion <p>The Se(B-CD-CA-4-NPs) complex represents a promising multifunctional therapeutic agent for GBM, offering enhanced proapoptotic property, selective tumor targeting, and reduced toxicity.</p>

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Effects of beta-cyclodextrin-Combretastatin A-4 nanoparticles containing selenium on apoptosis and metastasis of U-87MG glioblastoma cancer cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月2日

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  • Seyedeh Motahareh Hosseini,
  • Fatemehsadat Hosseini,
  • Elaheh Gheybi,
  • Elham Einafshar,
  • Ebrahim Eftekhar,
  • Mahmood Khayatian,
  • Mohammad Soukhtanloo

摘要

Background

Glioblastoma (GBM), the most aggressive primary brain tumor, faces significant treatment challenges due to drug resistance, blood–brain barrier limitations, and severe side effects of conventional therapies. This study aimed to develop and evaluate a nanotechnology-based therapeutic approach using selenium-loaded β-cyclodextrin-combretastatin A-4 nanoparticles (Se(B-CD-CA-4-NPs)) to overcome these limitations and enhance treatment efficacy.

Methods

The Se(B-CD-CA-4-NPs) complex was synthesized and characterized for morphology, size, stability, and selenium loading capacity. In vitro studies included MTT assay, cell apoptosis, scratch assay, gelatin zymography, and qPCR were used to assess the effect of the newly synthesized complex on U-87MG glioblastoma cell viability, cell death, migration, MMP-2 and MMP-9 activity, and mRNA expression level of apoptosis-related genes.

Results

The nanoparticles exhibited a spherical morphology (25.78 ± 3.4 nm), negative surface charge, and high stability. The IC50 of the synthesized complex was 1.629 μM in U-87MG cancer cells. The Se(B-CD-CA-4-NPs) complex significantly reduced U-87MG cell viability, migration and invasion. Additionally, the complex induced cell apoptosis via upregulation of the BAX/BCL-2 ratio in cancer cells. Moreover, the Se(B-CD-CA-4-NPs) complex inhibited metastasis by suppressing the activity and expression of MMP-2 and MMP-9.

Conclusion

The Se(B-CD-CA-4-NPs) complex represents a promising multifunctional therapeutic agent for GBM, offering enhanced proapoptotic property, selective tumor targeting, and reduced toxicity.