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Purpose <p>Doxorubicin (DOX), a widely used chemotherapeutic agent, demonstrates strong anticancer activity, but its clinical application is limited by systemic toxicity, poor solubility, and multidrug resistance. This study aimed to develop and optimize a mesoporous silica nanoparticle (MSN)-based drug delivery system to enhance the solubility, stability, and therapeutic efficacy of DOX against breast cancer.</p> Methods <p>MSNs Modified by Zn (Zinc), NH2 (Amine group), and Go (Graphene Oxide) (MSN-Zn-NH₂-GO (MZNG)). These nanoparticle were used to deliver DOX to breast cancer cells and evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), real-time PCR (Polymerase chain reaction), caspase activity, and ROS (Reactive oxygen species) assays.</p> Results <p>Characterization showed MZNG-DOX had a spherical, smooth surface with uneven distribution and an average diameter of ~ 215&#xa0;nm. The optimized formulation (F2) achieved a DOX entrapment efficiency (EE%) of 75.49 ± 1.33% and a loading content (LC%) of 9.15%. Cytotoxicity results demonstrated that free DOX was more biocompatible with HFF (Human foreskin fibroblast) cells compared to MZNG-DOX, while DOX-loaded nanoparticles significantly enhanced cytotoxicity against MDA-MB-231 (A triple-negative human breast adenocarcinoma cell line) cells compared with free drugs or non-loaded nanoparticles. Gene expression analysis revealed upregulation of <i>Bax</i>, <i>Caspase 3</i>, and <i>Mir-193</i>, and downregulation of <i>MMP-9 (Matrix metalloproteinase-9)</i> and <i>Bcl-2</i> following treatment. Furthermore, MZNG-DOX disrupted mitochondrial function, increasing ROS production and Caspase 3 activation in MDA-MB-231 cells.</p> Conclusion <p>These findings indicate that the developed nano-formulation not only improved the physicochemical properties of DOX but also significantly enhanced its anticancer efficacy. Overall MZNG-DOX nanoparticles demonstrate considerable promise as a strategy to overcome limitations of conventional DOX therapy and to improve breast cancer treatment outcomes.</p> Graphical Abstract <p></p>

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Mesoporous Silica Nanoparticles Modified with Zinc, Amine, and Graphene Oxide for Controlled Doxorubicin Delivery in Breast Cancer Therapy

  • 期刊论文

  • 发表日期：

    2026年5月7日

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  • Niyayesh Akhtari,
  • Seyedeh Elaheh Sheykholeslami,
  • Yeganeh Azari Incheh Sablagh,
  • Azadeh Mohammadgholi,
  • Afsoun Mansouri,
  • Hamid Abbasi,
  • Hassan Noorbazargan

摘要

Purpose

Doxorubicin (DOX), a widely used chemotherapeutic agent, demonstrates strong anticancer activity, but its clinical application is limited by systemic toxicity, poor solubility, and multidrug resistance. This study aimed to develop and optimize a mesoporous silica nanoparticle (MSN)-based drug delivery system to enhance the solubility, stability, and therapeutic efficacy of DOX against breast cancer.

Methods

MSNs Modified by Zn (Zinc), NH2 (Amine group), and Go (Graphene Oxide) (MSN-Zn-NH₂-GO (MZNG)). These nanoparticle were used to deliver DOX to breast cancer cells and evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), real-time PCR (Polymerase chain reaction), caspase activity, and ROS (Reactive oxygen species) assays.

Results

Characterization showed MZNG-DOX had a spherical, smooth surface with uneven distribution and an average diameter of ~ 215 nm. The optimized formulation (F2) achieved a DOX entrapment efficiency (EE%) of 75.49 ± 1.33% and a loading content (LC%) of 9.15%. Cytotoxicity results demonstrated that free DOX was more biocompatible with HFF (Human foreskin fibroblast) cells compared to MZNG-DOX, while DOX-loaded nanoparticles significantly enhanced cytotoxicity against MDA-MB-231 (A triple-negative human breast adenocarcinoma cell line) cells compared with free drugs or non-loaded nanoparticles. Gene expression analysis revealed upregulation of Bax, Caspase 3, and Mir-193, and downregulation of MMP-9 (Matrix metalloproteinase-9) and Bcl-2 following treatment. Furthermore, MZNG-DOX disrupted mitochondrial function, increasing ROS production and Caspase 3 activation in MDA-MB-231 cells.

Conclusion

These findings indicate that the developed nano-formulation not only improved the physicochemical properties of DOX but also significantly enhanced its anticancer efficacy. Overall MZNG-DOX nanoparticles demonstrate considerable promise as a strategy to overcome limitations of conventional DOX therapy and to improve breast cancer treatment outcomes.

Graphical Abstract