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<p>Improving the selectivity and safety of 5-fluorouracil (5-FU) remains a major challenge in cancer therapy, particularly due to its short systemic half-life, burst release in traditional carriers, and dose-dependent toxicity. To address these limitations, an eco friendly -synthesized nanocomposite composed of starch (S), polyethylene glycol (PEG), and cerium oxide (CeO₂) was developed as a stable and biocompatible platform for controlled 5-FU delivery. The hybrid system exhibited uniform nanoscale morphology (50&#xa0;nm by FESEM) and a stable hydrodynamic diameter of 193.48 ± 1.92&#xa0;nm with a positive surface charge of +40.71 ± 0.76 mV. High drug-loading performance was achieved, with a loading capacity of 53.00 ± 0.46% and an encapsulation efficiency of 87.50 ± 0.36%. The nanocarrier further demonstrated clear pH-responsive behavior, maintaining sustained drug retention at physiological pH (7.4) and accelerating drug diffusion under mildly acidic, tumor-like conditions (pH 5.4), reflecting a controlled and environment-sensitive release mechanism. The design of this nanocomposite integrates the swelling capability of the starch/PEG matrix with the inherent physicochemical properties of cerium oxide, producing a dual-functional hybrid with improved structural stability, enhanced drug retention, and selective delivery performance compared to conventional polymeric and inorganic systems. Collectively, the findings highlight the promise of the S/PEG/CeO₂ platform as an effective and biocompatible nanocarrier with potential translational relevance for safer and more efficient chemotherapeutic administration.</p>

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Eco-Friendly Synthesis of pH-Responsive Starch/PEG/CeO₂ Nanocomposites with Redox-Active Potential for Enhanced 5-Fluorouracil Delivery in Liver Cancer

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Fatemeh Mohamadzadeh,
  • Mehrab Pourmadadi,
  • Salar Mohammadi Shabestari

摘要

Improving the selectivity and safety of 5-fluorouracil (5-FU) remains a major challenge in cancer therapy, particularly due to its short systemic half-life, burst release in traditional carriers, and dose-dependent toxicity. To address these limitations, an eco friendly -synthesized nanocomposite composed of starch (S), polyethylene glycol (PEG), and cerium oxide (CeO₂) was developed as a stable and biocompatible platform for controlled 5-FU delivery. The hybrid system exhibited uniform nanoscale morphology (50 nm by FESEM) and a stable hydrodynamic diameter of 193.48 ± 1.92 nm with a positive surface charge of +40.71 ± 0.76 mV. High drug-loading performance was achieved, with a loading capacity of 53.00 ± 0.46% and an encapsulation efficiency of 87.50 ± 0.36%. The nanocarrier further demonstrated clear pH-responsive behavior, maintaining sustained drug retention at physiological pH (7.4) and accelerating drug diffusion under mildly acidic, tumor-like conditions (pH 5.4), reflecting a controlled and environment-sensitive release mechanism. The design of this nanocomposite integrates the swelling capability of the starch/PEG matrix with the inherent physicochemical properties of cerium oxide, producing a dual-functional hybrid with improved structural stability, enhanced drug retention, and selective delivery performance compared to conventional polymeric and inorganic systems. Collectively, the findings highlight the promise of the S/PEG/CeO₂ platform as an effective and biocompatible nanocarrier with potential translational relevance for safer and more efficient chemotherapeutic administration.