Potential of using cerium oxide nanoparticles for protecting healthy tissue during accelerated partial breast irradiation (APBI)

Abstract

The purpose of this study is to investigate the feasibility of using cerium oxide nanoparticles (CONPs) as radical scavengers during accelerated partial breast irradiation (APBI) to protect normal tissue. We hypothesize that CONPs can be slowly released from the routinely used APBI balloon applicators-via a degradable coating-and protect the normal tissue on the border of the lumpectomy cavity over the duration of APBI. To assess the feasibility of this approach, we analytically calculated the initial concentration of CONPs required to protect normal breast tissue from reactive oxygen species (ROS) and the time required for the particles to diffuse to various distances from the lumpectomy wall. Given that cerium has a high atomic number, we took into account the possible inadvertent dose enhancement that could occur due to the photoelectric interactions with radiotherapy photons. To protect against a typical MammoSite treatment fraction of 3.4Gy, 5ng·g(-1) of CONPs is required to scavenge hydroxyl radicals and hydrogen peroxide. Using 2nm sized NPs, with an initial concentration of 1mg·g(-1), we found that 2-10days of diffusion is required to obtain desired concentrations of CONPs in regions 1-2cm away from the lumpectomy wall. The resultant dose enhancement factor (DEF) is less than 1.01 under such conditions. Our results predict that CONPs can be employed for radioprotection during APBI using a new design in which balloon applicators are coated with the NPs for sustained/controlled in-situ release from within the lumpectomy cavity.

Keywords: APBI; Cerium oxide; Radiolysis; Radioprotectant.

Figure 1

Schematic of (1) water is exposed to 3.4 Gy of radiation, (2) the radiolysis of water produces ROS, namely OH^. and H₂O₂, (3) the removal of ROS from solution results in the oxidation of CONPs from Ce³⁺ to the Ce⁴⁺ state, (4) the auto-regeneration of the Ce³⁺ state. Please note: the chemical reactions depicted in this scheme are for conceptual purposes only; reaction mechanisms, intermediates, and products are not considered.

Figure 2

Schematic diagram of APBI using a balloon applicator coated with degradable polymer loaded with CONPs. Upon implantation of the balloon applicator, the CONPs are released into the surrounding tissue to provide protection from reactive oxygen species (ROS).

Figure 3

Tissue voxel model used for DEF calculation. The nanoparticles are assumed to be homogeneously distributed throughout the cells (V = 1000 μm³).

Figure 4

H₂O₂ (left axis) and OH· (right axis) production linearly increases with respect to radiation dose.

Figure 5

The concentration of CONPs needed to eliminate most ROS in the presence of a clinically relevant a radiation dose ranging from 0 to 6 Gy.

Figure 6

CONP concentrations at distances ranging 0–2 cm from the initial source. Three sizes of nanoparticles were considered: 2, 5, and 10 nm. 5 ng-g⁻¹ of CONPs were needed to eliminate ROS in the presence of 3.4 Gy. The values were obtained after seven days of diffusion.

Figure 7

Number of days need to achieve a CONP concentration (≥0.005 mg-g⁻¹) adequate to protect the tissue at a depth of 1, 1.5, and 2 cm.

Figure 8

DEF due to 0.645 mg-g⁻¹ CONP with respect kVp radiation is less than 1.01.

Figure 9

DEF is linear with respect to CONP concentration at 60, 100, and 120 kVp.