Breast radiotherapy with kilovoltage photons and gold nanoparticles as radiosensitizer: An in vitro study

Abstract

We investigated the dose enhancement and internalization of gold nanoparticles (AuNPs) used as a radiosensitizer agent for rotational radiotherapy of breast cancer using a kilovoltage (kV) X-ray beam. Methods: Human breast cancer cells MDA-MB-231 were incubated with or without 100 μg/mL (4.87 nM) or 200 μg/mL (9.74 nM) 15 nm AuNPs and irradiated with 100 kV, 190 kV, or 6 MV X-rays. To assess the toxicity of the AuNPs, we performed a Sulforhodamine B assay. Using atomic absorption spectroscopy, scanning electron microscopy, transmission electron microscopy, and time-lapse optical microscopy (rate of 2 frames per minute), we carried out a quantitative assessment of the amount of gold internalized by MDA-MB-231 cells and a characterization of the static and dynamical aspects of this internalization process. Results: No effect of AuNPs alone was shown on cell viability. Time-lapse optical microscopy showed for the first time AuNPs cellular uptake and the dynamics of AuNPs internalization. Electron microscopy demonstrated AuNPs localization in endosomal vesicles, preferentially in the perinuclear region. After irradiation at doses up to 2 Gy, cell survival fraction curves showed increased mortality with AuNPs, with respect to irradiation without AuNPs. The highest effect of radioenhancement by AuNPs (at 9.74 nM AuNPs concentration) was observed at 190 kV showing a dose enhancement factor of 1.33 ± 0.06 (1.34 ± 0.02 at 100 kV), while at 6 MV it was 1.14 ± 0.06. Conclusions: The observed radio-sensitization effect is promising for future radio-enhanced kV radiotherapy of breast cancer and quantitatively in the order of previous observations for 15 nm AuNPs. These results of a significant dose enhancement were obtained at 15 nm AuNPs concentration as low as several nanomolar units, at dose levels typical of a single dose fraction in a radiotherapy session. Dynamical behavior of the 3D spatial distribution of 15 nm AuNPs outside the nucleus of single breast cancer cell was observed, with possible implications for future models of AuNPs sensitization.

Consolidation of Gold and Gadolinium Nanoparticles: An Extra Step towards Improving Cancer Imaging and Therapy

“…A dose increase was observed with the increase in mass concentration of gold in the nanoparticles for all shapes and both nanorod sizes; however, two-dimensional AuNPs provided superior in terms of radioenhancement with external radiation therapy compared to the nanorods for both 6 MV and 18 MV X-ray irradiation [46]. Tudda et al achieved a significant dose enhancement via AuNPs during rotational radiotherapy of MDA-MB-231 breast cancer cells using X-ray beam kV photons [47]. A total of 15 nm AuNPs of 100 µg/mL (4.87 nM) and 200 µg/mL (9.74 nM) were prepared for radiosensitization of the cancer cells, which were subjected to 100 kV, 190 kV, and 6 MV X-rays [47].…”

“…Tudda et al achieved a significant dose enhancement via AuNPs during rotational radiotherapy of MDA-MB-231 breast cancer cells using X-ray beam kV photons [47]. A total of 15 nm AuNPs of 100 µg/mL (4.87 nM) and 200 µg/mL (9.74 nM) were prepared for radiosensitization of the cancer cells, which were subjected to 100 kV, 190 kV, and 6 MV X-rays [47]. Following irradiation up until 2 Gy, cells incubated with AuNPs showed a decrease in viability compared to the cells without AuNPs, while the most significant radiosensitization effect was observed at the concentration of 9.74 nM, with the 190 kV beam obtaining a DEF of 1.33 ± 0.06 [47].…”

Recent Metal Nanotheranostics for Cancer Diagnosis and Therapy: A Review

“…One pioneering in-vivo study was conducted by Herold et al [19] in 2000 when it was first reported that gold microspheres could produce radiation dose enhancement against tumors using kilovoltage X-rays. Tudda et al reported that 15 nm AuNPs could produce biologically effective dose enhancement in rotational radiotherapy of breast cancer using kilovoltage X-rays [20]. Luan et al [21] described an improvement in the radio-therapeutic efficiency in the treatment of esophageal tumor-bearing mice following the delivery of AuNPs to tumors.…”

Nanomaterials as Theranostic Agents for Cancer Therapy

“…Herold et al first reported in 2000 that gold microspheres could construct radiation dose enhancement in opposition to tumors when using KV X-rays . Tudda et al reported that KV X-rays in rotational breast cancer radiotherapy exhibited biologically effective dose enhancement through the application of 15 nm AuNPs . In another study by Luan et al, enhancement in the radiotherapeutic effectiveness was seen in the treatment of esophageal tumor-bearing mice after the delivery of AuNPs to tumors .…”

“…111 Tudda et al reported that KV X-rays in rotational breast cancer radiotherapy exhibited biologically effective dose enhancement through the application of 15 nm AuNPs. 112 In another study by Luan et al, enhancement in the radiotherapeutic effectiveness was seen in the treatment of esophageal tumor-bearing mice after the delivery of AuNPs to tumors. 99 The radiosensitization efficiency of AuNPs was affected by particle type, radiation parameters, and cell type.…”