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<p>We introduce a simple, equipment-free route to fabricate silk fibroin–chitosan (SF–CS) hybrid nanoparticles (NPs) that purposefully upgrade chitosan carriers for doxorubicin (DOX) delivery by leveraging silk’s intrinsic biocompatibility and its multi-modal drug–polymer interactions. Silk fibroin contributes hydrophobic β-sheet and hydroxyl/carbonyl groups that can engage DOX through hydrophobic, hydrogen-bonding, and electrostatic interactions, a design intended to enhance loading and govern release. By varying the chitosan fraction during synthesis, we established composition–property maps showing tunable particle size and zeta potential. The NPs synthesized with 2% and 0.3% w/v of SF and CS (designated as NP3), achieved a small dry diameter by scanning electron microscopy (16.5 ± 4.1&#xa0;nm) with a larger hydrodynamic diameter (≈ 85.4&#xa0;nm), and exhibited a strongly positive surface charge ( ≈ + 25 mV). NP3 enabled efficient DOX entrapment (entrapment efficiency = 53.7 ± 3.5%; loading capacity = 20.8 ± 1.1% w/w) and pH-responsive release with accelerated liberation under acidic conditions relevant to the tumor/endosomal milieu. In vitro, SF–CS formulations—particularly NP3—showed enhanced cellular uptake and nuclear accumulation of DOX, translating into stronger cytotoxic activity compared with chitosan nanoparticle. Collectively, these results demonstrate that introducing silk as a functional additive furnishes small, charge-tunable nano particles for chemotherapy and related biomedical applications.</p> Graphical abstract <p></p>

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Facile Fabrication of Silk Fibroin–Chitosan Hybrid Nanoparticles for Doxorubicin Delivery to Breast Cancer Cells

  • 期刊论文

  • 发表日期：

    2026年7月30日

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  • Negar Bahramian,
  • Fatemeh Bagheri,
  • Amir Hossein Mohammadi

摘要

We introduce a simple, equipment-free route to fabricate silk fibroin–chitosan (SF–CS) hybrid nanoparticles (NPs) that purposefully upgrade chitosan carriers for doxorubicin (DOX) delivery by leveraging silk’s intrinsic biocompatibility and its multi-modal drug–polymer interactions. Silk fibroin contributes hydrophobic β-sheet and hydroxyl/carbonyl groups that can engage DOX through hydrophobic, hydrogen-bonding, and electrostatic interactions, a design intended to enhance loading and govern release. By varying the chitosan fraction during synthesis, we established composition–property maps showing tunable particle size and zeta potential. The NPs synthesized with 2% and 0.3% w/v of SF and CS (designated as NP3), achieved a small dry diameter by scanning electron microscopy (16.5 ± 4.1 nm) with a larger hydrodynamic diameter (≈ 85.4 nm), and exhibited a strongly positive surface charge ( ≈ + 25 mV). NP3 enabled efficient DOX entrapment (entrapment efficiency = 53.7 ± 3.5%; loading capacity = 20.8 ± 1.1% w/w) and pH-responsive release with accelerated liberation under acidic conditions relevant to the tumor/endosomal milieu. In vitro, SF–CS formulations—particularly NP3—showed enhanced cellular uptake and nuclear accumulation of DOX, translating into stronger cytotoxic activity compared with chitosan nanoparticle. Collectively, these results demonstrate that introducing silk as a functional additive furnishes small, charge-tunable nano particles for chemotherapy and related biomedical applications.

Graphical abstract