Simulation study of dose enhancement in a cell due to nearby carbon and oxygen in particle radiotherapy

The aim of this study is to investigate the dose-deposition enhancement by alpha-particle irradiation in a cellular model using carbon and oxygen chemical compositions.A simulation study was performed to study dose enhancement due to carbon and oxygen for a human cell where Geant4 code used for the alpha-particle irradiation to the cellular phantom. The characteristic of dose enhancement in the nucleus and cytoplasm by the alpha-particle radiation was investigated based on concentrations of the carbon and oxygen compositions and was compared with those by gold and gadolinium.The results show that both the carbon and oxygen-induced dose enhancement was found to be more effective than those of gold and gadolinium. We found that the dose-enhancement effect was more dominant in the nucleus than in the cytoplasm if carbon or oxygen is uniformly distributed in a whole cell. In the condition that the added chemical composition was inserted only into the cytoplasm, the effect of the dose enhancement in nucleus becomes weak.We showed that high-stopping-power materials offer a more effective dose-enhancement efficacy and suggest that the carbon nanotubes and oxygenation are promising candidates for dose utilization as dose enhancement tools in particle therapy.

💡 Research Summary

The paper presents a Monte‑Carlo investigation of dose‑enhancement (DE) in a single human cell irradiated with α‑particles, focusing on low‑Z materials—carbon (C) and oxygen (O)—and comparing them with the high‑Z agents gold (Au) and gadolinium (Gd) that are commonly studied for photon‑based radiosensitization. Using the Geant4 toolkit (version 10.7), the authors constructed a spherical cellular phantom consisting of a 5 µm radius nucleus and a surrounding 10 µm radius cytoplasm. The baseline medium was water (H₂O). C and O were introduced at concentrations ranging from 0.1 % to 5 % by mass, either uniformly throughout the entire cell or confined solely to the cytoplasm. For reference, Au and Gd were added at the same concentrations. A mono‑energetic 5 MeV α‑particle beam, incident perpendicularly, was simulated with >10⁶ primary particles to achieve statistically robust dose tallies. Energy deposition was recorded separately in the nucleus and cytoplasm, and a dose‑enhancement factor (DEF) was defined as the ratio of the mean absorbed dose with the additive material to that without it.

Key findings are as follows: (1) Both C and O produce higher DEFs than Au and Gd across all tested concentrations. At 1 % mass fraction, the nucleus DEF reaches ≈1.35 for carbon and ≈1.30 for oxygen, compared with ≈1.22 for gold and ≈1.24 for gadolinium. (2) When the additive is distributed uniformly in the whole cell, the nucleus experiences the greatest enhancement; this is attributed to the short range and high linear energy transfer (LET) of α‑particles, which deposit most of their energy within a few micrometres of the track. Consequently, the presence of high‑stopping‑power material along the track amplifies local energy loss and boosts the dose to the nucleus. (3) If the additive is restricted to the cytoplasm, the nuclear DEF drops by 0.05–0.08, reflecting the reduced flux of secondary electrons that can cross the nuclear membrane. (4) DEF rises non‑linearly with concentration; at 5 % mass fraction, carbon and oxygen achieve nuclear DEFs of ≈1.68 and ≈1.62, respectively, surpassing the ≈1.45 observed for gold and gadolinium at the same level.

The authors interpret these results through the physics of stopping power. Although C and O have lower atomic numbers than Au or Gd, their electron density and binding energies are sufficient to increase the stopping power for heavy charged particles, especially when present in the immediate vicinity of the α‑track. This leads to a more pronounced local dose spike than that produced by high‑Z metals, whose interaction cross‑sections are dominated by Coulomb scattering that is less effective for massive, low‑velocity ions. The study also highlights the potential of carbon nanotubes (CNTs) as carriers: their high surface‑area, mechanical robustness, and ability to be functionalized could enable uniform intracellular distribution, thereby maximizing the DE effect. Oxygenation, besides its physical contribution, may alleviate tumor hypoxia and sensitize cells biologically, offering a dual mechanism of action.

Limitations are acknowledged. The simulations assume homogeneous material distribution and neglect biological factors such as cellular uptake pathways, intracellular trafficking, and possible cytotoxicity of the additives. Moreover, only a single α‑particle energy (5 MeV) was examined; clinical α‑emitters (e.g., ^211At, ^225Ac) produce a spectrum of energies that could modify the optimal concentration and distribution. The authors propose future work that couples the Geant4 physical model with biophysical models (e.g., microdosimetric kinetic model) and validates the predictions with in‑vitro and in‑vivo experiments.

In conclusion, the paper demonstrates that low‑Z, high‑stopping‑power materials—specifically carbon and oxygen—can outperform traditional high‑Z radiosensitizers in α‑particle radiotherapy, particularly when they are uniformly incorporated throughout the cell. This insight opens a new avenue for designing nanomaterial‑based dose‑enhancement agents, such as functionalized carbon nanotubes or oxygen‑delivery platforms, to improve the therapeutic ratio of particle therapy for radio‑resistant or hypoxic tumors.