Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy

Figures & data

Table 1 Treatment Components for the Radiosensitization Effect Study

Treatment	Components
Radiation dose (Gy)	0 (positive control), 1, 2, 3, 4
Negative control	Untreated with BiONPs or Cis
Radiation + BiONPs	Radiation + 0.5 mM BiONPs
Radiation + Cis	Radiation + 1.30 µM Cis
Radiation + BC	Radiation + 0.5 mM BiONPs + 1.30 µM Cis

Abbreviations: cGy, centigray; BiONPs, bismuth oxide nanoparticles; Cis, cisplatin; BC, BiONPs-Cis combination.

Figure 1 Theoretical dose enhancement factor (DEF) of each component at various energy ranges, with brachytherapy range at 0.38 MeV.

Notes: DEF of Cis and BiONPs is interpolated using the Sm and Pt database. The percentage of each component depended on the volume used during the irradiation.

Abbreviations: Zeff, effective atomic number; Sm, Samarium; Pt; platinum.

Figure 2 Percentage of cell viability after treatment with 60 nm BiONPs of different concentrations for 24, 48, and 72 hrs, on (A) MCF-7, (B) MDA-MB-231 and (C) NIH/3T3 cells.

Notes: Error bars represent the standard error of the mean (SEM).

Abbreviation: BiONPs, bismuth oxide nanoparticles.

Figure 3 Localisation of BiONPs near the nuclei inside the (A) MCF-7, (B) MDA-MB-231 and (C) NIH/3T3 cells, after 24 hrs of incubation with 0.5 mMol/L of the BiONPs.

Notes: Arrows indicated the rod-shaped BiONPs. The scale of each picture is 20 µm.

Abbreviation: BiONPs, bismuth oxide nanoparticles.

Figure 4 Cytotoxic evaluation of cisplatin against MCF-7, MDA-MB-231, and NIH/3T3 cell lines. Each point shows the percentage of viable cells in comparison to the negative control. Curves are fitted using the Dose-Response model.

Notes: Error bars represent the standard error of the mean (SEM).

Table 2 Radiobiological Analysis Based on Linear Quadratic Models Corresponding to Figure 6

Cell		Control	BiONPs	Cis	BC
MCF-7	α	0.35 ± 0.02	0.62 ± 0.13	0.62 ± 0.10	1.56 ± 0.14
	β	0.00 ± 0.01	−0.04 ± 0.04	−0.02 ± 0.03	−0.16 ± 0.04
	SER	1.00	1.67	1.70	4.29
MDA-MB-231	α	0.26 ± 0.03	0.52 ± 0.07	0.44 ± 0.13	0.22 ± 0.02
	β	0.08 ± 0.01	−0.06 ± 0.02	0.04 ± 0.04	0.29 ± 0.01
	SER	1.00	1.03	1.22	1.41
NIH/3T3	α	0.12 ± 0.15	−0.02 ± 0.06	0.27 ± 0.10	0.59 ± 0.06
	β	0.09 ± 0.06	0.10 ± 0.02	−0.02 ± 0.03	−0.04 ± 0.02
	SER	1.00	0.77	0.66	1.65

Notes: Control represents radiation treatment only.

Abbreviations: SER, sensitization enhancement ratio; cGy, centigray; BiONPs, bismuth oxide nanoparticles; Cis, cisplatin; BC, the combination of BiONPs and Cis.

Figure 5 Survival curves of control, BiONPs, Cis, and BC treated on (A) MCF-7, (B) MDA-MB-231 and (C) NIH/3T3 cells irradiated with HDR brachytherapy. The survival data were fitted to linear-quadratic (LQ) models.

Notes: Error bars represent the standards errors of survival fractions.

Figure 6 Comparison of theoretical DEF and experimental SER in MCF-7, MDA-MB-231, and NIH/3T3 cells.

Note: Theoretical DEF values are obtained from Figure 1.

Abbreviations: DEF, dose enhancement ratio; SER, sensitization enhancement ratio; BiONPs, bismuth oxide nanoparticles; Cis, cisplatin; BC, BiONPs-Cis combination.

Figure 7 Reactive oxygen species (ROS) generation on (A) MCF-7, (B) MDA-MB-231 and (C) NIH/3T3 cells that underwent brachytherapy irradiation in the presence of BiONPs, Cis, and BC.

Notes: Error bars represent the errors of survival fractions.