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Purpose <p>Colorectal cancer is a leading global cancer with treatment challenges due to radioresistance. Radiosensitizers have emerged as promising agents to enhance the efficacy of radiotherapy by increasing the sensitivity of cancer cells to radiation. Among these, Schiff Base Iron Complexes (Fe-L4) are novel candidates with potential radiosensitization properties. This study investigates the effects of Fe-L4 nanoparticles (Fe-L4 NPs) on human colorectal carcinoma (HCT 116) cells under cobalt-60 (Co-60) brachytherapy, aiming to improve therapeutic outcomes in localized cancer treatment.</p> Methods <p>The cytotoxicity of Fe‑L4 NPs was assessed in HCT116 cells using the PrestoBlue assay to determine the inhibitory concentration at 80% viability (IC20), which was then used for subsequent experiments. Cells were treated with Fe‑L4 NPs and irradiated with Co‑60 HDR brachytherapy doses ranging from 0 to 5&#xa0;Gy. Clonogenic survival assays were performed, and cell survival data were analyzed using a linear–quadratic (LQ) model to derive survival parameters with and without Fe‑L4 treatment. Dose verification was conducted with radiochromic film to ensure accurate dose delivery.</p> Results <p>The IC20 of Fe‑L4 NPs was determined to be 0.12&#xa0;mg/mL. Clonogenic assays showed a significant reduction in surviving fraction for cells treated with Fe‑L4 NPs compared to controls at all dose levels, demonstrating enhanced radiosensitivity. The sensitizer enhancement ratio (SER) at 50% survival (D₅₀) was calculated to be 1.21, indicating a 21% increase in radiosensitivity with Fe‑L4 NPs. Additionally, LQ model analysis revealed higher α/β ratios for Fe‑L4 NP-treated cells, supporting increased DNA damage and reduced repair capability.</p> Conclusions <p>Fe‑L4 nanoparticles significantly enhanced the radiosensitivity of HCT116 colorectal cancer cells under HDR Co‑60 brachytherapy conditions, suggesting their potential to improve therapeutic outcomes by widening the therapeutic ratio. Further studies, including mechanistic analyses and in vivo validation, are recommended to elucidate the underlying pathways and assess clinical translatability.</p>

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Radiosensitization effect of Schiff Base Iron (III) Complex (Fe‑L4) on human colon carcinoma cells irradiated with HDR Co‑60 brachytherapy

  • 期刊论文

  • 发表日期：

    2025年7月17日

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  • N. A. M. Chipto,
  • W. N. Rahman,
  • T. A. F. T. Ahmad,
  • R. A. Rashid,
  • M. Algethami,
  • A. S. Assran,
  • Z. Jamalludin

摘要

Purpose

Colorectal cancer is a leading global cancer with treatment challenges due to radioresistance. Radiosensitizers have emerged as promising agents to enhance the efficacy of radiotherapy by increasing the sensitivity of cancer cells to radiation. Among these, Schiff Base Iron Complexes (Fe-L4) are novel candidates with potential radiosensitization properties. This study investigates the effects of Fe-L4 nanoparticles (Fe-L4 NPs) on human colorectal carcinoma (HCT 116) cells under cobalt-60 (Co-60) brachytherapy, aiming to improve therapeutic outcomes in localized cancer treatment.

Methods

The cytotoxicity of Fe‑L4 NPs was assessed in HCT116 cells using the PrestoBlue assay to determine the inhibitory concentration at 80% viability (IC20), which was then used for subsequent experiments. Cells were treated with Fe‑L4 NPs and irradiated with Co‑60 HDR brachytherapy doses ranging from 0 to 5 Gy. Clonogenic survival assays were performed, and cell survival data were analyzed using a linear–quadratic (LQ) model to derive survival parameters with and without Fe‑L4 treatment. Dose verification was conducted with radiochromic film to ensure accurate dose delivery.

Results

The IC20 of Fe‑L4 NPs was determined to be 0.12 mg/mL. Clonogenic assays showed a significant reduction in surviving fraction for cells treated with Fe‑L4 NPs compared to controls at all dose levels, demonstrating enhanced radiosensitivity. The sensitizer enhancement ratio (SER) at 50% survival (D₅₀) was calculated to be 1.21, indicating a 21% increase in radiosensitivity with Fe‑L4 NPs. Additionally, LQ model analysis revealed higher α/β ratios for Fe‑L4 NP-treated cells, supporting increased DNA damage and reduced repair capability.

Conclusions

Fe‑L4 nanoparticles significantly enhanced the radiosensitivity of HCT116 colorectal cancer cells under HDR Co‑60 brachytherapy conditions, suggesting their potential to improve therapeutic outcomes by widening the therapeutic ratio. Further studies, including mechanistic analyses and in vivo validation, are recommended to elucidate the underlying pathways and assess clinical translatability.