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<p>Recent advances in nanotechnology-based cancer therapy have underscored the potential of natural polysaccharides such as chitosan (CS) and agarose (Aga) for targeted and biocompatible drug delivery applications. In this study, a novel CS/Aga/ZnO@DOX nanocomposite was synthesized via a double water-in-oil-in-water (W/O/W) emulsification approach to improve the delivery efficiency and therapeutic performance of doxorubicin (DOX) against U87-MG brain cancer cells. The structural, morphological, and physicochemical characteristics of the prepared nanocomposites were confirmed through Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), and zeta-potential analyses. The nanocomposite displayed a uniform semi-spherical morphology, high colloidal stability with a zeta potential of + 48.37 mV, and an average hydrodynamic diameter of approximately 300&#xa0;nm. Incorporation of Zinc oxide (ZnO) enhanced drug loading and encapsulation efficiency by 9% and 22.5%, respectively, which can be attributed to strengthened hydrogen bonding interactions and improved matrix stability. In vitro release studies revealed a clear pH-responsive behavior, with 96.25% DOX release at pH 5.4 compared with 63% at pH 7.4, indicating selective drug release under tumor-like acidic conditions. Kinetic analysis demonstrated that the Higuchi model best fit the release data at pH 5.4 (R² = 0.9925), suggesting a diffusion-controlled mechanism. The MTT assay confirmed selective cytotoxicity, showing 49% viability in U87-MG cells and 81% in normal L929 fibroblasts, compared with 64% viability for free DOX. These results indicate enhanced therapeutic efficiency alongside reduced off-target toxicity. Altogether, the CS/Aga/ZnO@DOX nanocomposite exhibits structural stability, high encapsulation efficiency, and controlled pH-responsive release, making it a promising candidate for targeted and localized brain cancer therapy with minimized systemic side effects.</p>

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pH-Responsive Chitosan–Agarose/ZnO Hybrid Nanocomposites for Controlled Doxorubicin Release and Targeted Brain Cancer Therapy

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Mehrab Pourmadadi,
  • Pooya biglari,
  • Salar Mohammadi Shabestari,
  • Roya Yaghoobi,
  • Narges Ajalli,
  • Mohammadamin Hashemipour,
  • Mahrokh Bahramian,
  • Iman Ghaderi,
  • Mohammadamin ghasem Mehrabi,
  • Fariborz Sharifianjazi

摘要

Recent advances in nanotechnology-based cancer therapy have underscored the potential of natural polysaccharides such as chitosan (CS) and agarose (Aga) for targeted and biocompatible drug delivery applications. In this study, a novel CS/Aga/ZnO@DOX nanocomposite was synthesized via a double water-in-oil-in-water (W/O/W) emulsification approach to improve the delivery efficiency and therapeutic performance of doxorubicin (DOX) against U87-MG brain cancer cells. The structural, morphological, and physicochemical characteristics of the prepared nanocomposites were confirmed through Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), and zeta-potential analyses. The nanocomposite displayed a uniform semi-spherical morphology, high colloidal stability with a zeta potential of + 48.37 mV, and an average hydrodynamic diameter of approximately 300 nm. Incorporation of Zinc oxide (ZnO) enhanced drug loading and encapsulation efficiency by 9% and 22.5%, respectively, which can be attributed to strengthened hydrogen bonding interactions and improved matrix stability. In vitro release studies revealed a clear pH-responsive behavior, with 96.25% DOX release at pH 5.4 compared with 63% at pH 7.4, indicating selective drug release under tumor-like acidic conditions. Kinetic analysis demonstrated that the Higuchi model best fit the release data at pH 5.4 (R² = 0.9925), suggesting a diffusion-controlled mechanism. The MTT assay confirmed selective cytotoxicity, showing 49% viability in U87-MG cells and 81% in normal L929 fibroblasts, compared with 64% viability for free DOX. These results indicate enhanced therapeutic efficiency alongside reduced off-target toxicity. Altogether, the CS/Aga/ZnO@DOX nanocomposite exhibits structural stability, high encapsulation efficiency, and controlled pH-responsive release, making it a promising candidate for targeted and localized brain cancer therapy with minimized systemic side effects.