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Background <p>Radiotherapy (RT) remains a cornerstone of Breast cancer (BC) treatment, but its effectiveness is hindered by challenges such as tumor hypoxia and lack of selectivity. Nanoparticles (NPs), especially those composed of high-Z materials like bismuth oxide (Bi₂O₃), have emerged as promising radiosensitizers to enhance RT efficacy.</p> Objective <p>This study aims to compare the radiosensitizing effects of two functionalized Bi₂O₃-based NPs, chitosan (CS)-coated Bi₂O₃ NPs conjugated with 5-aminolevulinic acid and curcumin (Bi₂O₃/CS@5-ALA-CUR), and β-cyclodextrin (PCD)-coated Bi₂O₃ NPs conjugated with curcumin and glucose (Bi₂O₃@PCD-CUR-Glu), for targeted BC RT.</p> Methods <p>Two Bi₂O₃-based NP formulations were synthesized and characterized for size, surface charge, and drug loading. Then, NPs were characterized fully. Their radiosensitizing effects were tested in-vitro using SKBr-3 and NIH3T3 cells, assessing cytotoxicity, reactive oxygen species (ROS) generation, and migration inhibition. In-vivo tumor growth inhibition was evaluated in a BALB/c mouse model with 6 MV X-rays (2&#xa0;Gy) irradiation.</p> Results <p>Both NP formulations exhibited high biocompatibility and selective cytotoxicity towards SKBr-3 cells, reducing cell viability by 60–69% at 160&#xa0;µg/mL. Bi₂O₃/CS@5-ALA-CUR NPs showed superior radiosensitization, reducing cell viability by 64% under 2&#xa0;Gy irradiation. The functionalized NPs enhanced ROS generation, alleviated hypoxia (reducing hypoxic cell viability by 17%), and inhibited migration. In-vivo, Bi₂O₃/CS@5-ALA-CUR NPs combined with 2&#xa0;Gy irradiation reduced tumor volume by 64%, compared to a 50% reduction with Bi₂O₃@PCD-CUR-Glu NPs.</p> Conclusion <p>The study demonstrates that Bi₂O₃/CS@5-ALA-CUR NPs are more effective radiosensitizers than Bi₂O₃@PCD-CUR-Glu NPs in BC RT. These findings highlight the potential of modified Bi₂O₃ NPs in overcoming the limitations of traditional RT, providing a promising approach for improving treatment outcomes in BC.</p> Graphical abstract <p></p>

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Synergistic radiosensitization of breast cancer using bismuth oxide nanoparticles coated with chitosan and β-cyclodextrin loaded with curcumin and 5-aminolevulinic acid

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Masoumeh Dastgir,
  • Yasin Ayyami,
  • Marjan Ghorbani,
  • Maedeh Yektamanesh,
  • Amir Ghasemi Jangjoo,
  • Hamed Zamani,
  • Soheila Sharifian Jazzi,
  • Omid Abouie Mehrizi,
  • Tohid Mortezazadeh,
  • Reza Malekzadeh

摘要

Background

Radiotherapy (RT) remains a cornerstone of Breast cancer (BC) treatment, but its effectiveness is hindered by challenges such as tumor hypoxia and lack of selectivity. Nanoparticles (NPs), especially those composed of high-Z materials like bismuth oxide (Bi₂O₃), have emerged as promising radiosensitizers to enhance RT efficacy.

Objective

This study aims to compare the radiosensitizing effects of two functionalized Bi₂O₃-based NPs, chitosan (CS)-coated Bi₂O₃ NPs conjugated with 5-aminolevulinic acid and curcumin (Bi₂O₃/CS@5-ALA-CUR), and β-cyclodextrin (PCD)-coated Bi₂O₃ NPs conjugated with curcumin and glucose (Bi₂O₃@PCD-CUR-Glu), for targeted BC RT.

Methods

Two Bi₂O₃-based NP formulations were synthesized and characterized for size, surface charge, and drug loading. Then, NPs were characterized fully. Their radiosensitizing effects were tested in-vitro using SKBr-3 and NIH3T3 cells, assessing cytotoxicity, reactive oxygen species (ROS) generation, and migration inhibition. In-vivo tumor growth inhibition was evaluated in a BALB/c mouse model with 6 MV X-rays (2 Gy) irradiation.

Results

Both NP formulations exhibited high biocompatibility and selective cytotoxicity towards SKBr-3 cells, reducing cell viability by 60–69% at 160 µg/mL. Bi₂O₃/CS@5-ALA-CUR NPs showed superior radiosensitization, reducing cell viability by 64% under 2 Gy irradiation. The functionalized NPs enhanced ROS generation, alleviated hypoxia (reducing hypoxic cell viability by 17%), and inhibited migration. In-vivo, Bi₂O₃/CS@5-ALA-CUR NPs combined with 2 Gy irradiation reduced tumor volume by 64%, compared to a 50% reduction with Bi₂O₃@PCD-CUR-Glu NPs.

Conclusion

The study demonstrates that Bi₂O₃/CS@5-ALA-CUR NPs are more effective radiosensitizers than Bi₂O₃@PCD-CUR-Glu NPs in BC RT. These findings highlight the potential of modified Bi₂O₃ NPs in overcoming the limitations of traditional RT, providing a promising approach for improving treatment outcomes in BC.

Graphical abstract