Fe/57Fe-Metallacarboranes with Radiosensitizing Potential in Breast Cancer Cell Models: Comparative Study Between High- (60Co) and Low-Energy (57Co) Gamma Radiation Sources

TL;DR

This study explores how a new compound, Fe/57Fe-ferrabisdicarbollide, can enhance cancer cell destruction using low-dose radiation, potentially leading to safer cancer treatments.

Contribution

The study introduces a novel radiosensitizing compound that enables effective cancer therapy with lower radiation doses.

Findings

Low-dose 57Co radiation combined with the compound significantly reduced cancer cell viability and survival in 3D spheroid models.

The radiosensitizing effect is attributed to localized dose enhancement via the Mössbauer effect and high LET electrons.

3D spheroid models showed greater radiosensitization compared to 2D models.

Abstract

Background: Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/57Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose 60Co (2.08 Gy) and low-dose 57Co (37.55 mGy, 57Fe Mössbauer effect). Methods: We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. Results: In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose 57Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the Mössbauer effect, where the resonant absorption of 14.41 keV radiation by 57Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Conclusions: Fe/57Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments.

Figures