Multifunction bismuth gadolinium oxide nanoparticles as radiosensitizer in radiation therapy and imaging

Abstract

Multifunction bismuth-based nanoparticles with the ability to display diagnostic and therapeutic functions have drawn extensive attention as theranostic agents in radiation therapy and imaging due to their high atomic number, low toxicity, and low cost. Herein, we tried to introduce multifunction bismuth gadolinium oxide nanoparticles (BiGdO3) as a new theranostic agent for radiation therapy, computed tomography (CT) and magnetic resonance imaging (MRI). After synthesis of BiGdO3 nanoparticles and surface modifications of them with PEG, biocompatibility of the nanoparticles was evaluated by a CCK-8 assay. We investigated dose amplification properties of the nanoparticles using gel dosimetry and in vitro and in vivo assays. According to clonogenic assay radiation, a sensitizer enhancement ratio (SER) of 1.75 and 1.66 (100 µg ml−1-nanoparticles), for MCF-7 and 4T1 cell lines at low energy x-ray was achieved, respectively. Radiation dose enhancement effect of the nanoparticles was proven for high concentrations (500 µg ml−1) by gel dosimetry. For further investigation, in vivo cancer radiotherapy was carried out using female BALB/c mice with 4T1 breast tumors. In vivo results emphasized the radiosensitizing effect of BiGdO3-PEG nanoparticles. Both bismuth and gadolinium provide CT contrast, while gadolinium can be employed for MRI T1 contrast, so we evaluated contrast enhancement of BiGdO3-PEG nanoparticles as a dual-modal imaging agent in MR and CT imaging. Collectively, our experimental results clearly display properties of BiGdO3-PEG nanoparticles as multimodal imaging and radiosensitizing agents. The results show that the nanoparticles deserve further study as a new theranostic agent.

Galvanic replacement reaction for in situ fabrication of litchi-shaped heterogeneous liquid metal-Au nano-composite for radio-photothermal cancer therapy

“…It is generally recognized that materials with high atomic numbers can effectively convert the X-ray radiation energy by means of excellent X-ray absorption coefficient to produce secondary electrons for radiosensitization [ 53 , 54 ]. The dose enhancement ability of radiosensitizer is a significant parameters to evaluate radiotherapy effect, which can be tested by gel dosimetry protocol [ 42 ]. In this study, the modified MAGIC gel dosimetry developed by Fong [ 55 ] was used to evaluate the dose enhancement contributed by both samples under different radiation densities.…”

“…According to a typical method [ 41 , 42 ], the gelatin (2.08 g) was added into DI water (19.57 mL) under stirring at 50 °C, and hydroquinone solution (0.04 g/mL, 1 mL) was then dropped into gelatin solution when the gelatin dissolved completely. Afterward, the methacrylic acid (1.5 mL), ascorbic acid (0.0075 g), and copper sulphate powder (0.005 g) were added into above mixture solution and stirred for 10 min.…”

The versatile biomedical applications of bismuth-based nanoparticles and composites: therapeutic, diagnostic, biosensing, and regenerative properties

“…384 Using heavy metal nano-radiosensitizers is a helpful approach to enhance the therapeutic efficiency of RT without increasing radiation doses to dangerously high levels that can non-selectively affect the normal function of surrounding tissues. 385 BiNPs are used for this aim because of their strong photoelectric absorption and high generation of secondary electrons under radiation exposure. [386][387][388][389] Huang et al 353 constructed a brachytherapy platform based on Bi 2 S 3 encapsulated PLGA nanocapsules (Bi 2 S 3 @PLGA) using a water/oil/water (W/O/W) emulsion approach.…”

Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy

“…Finally, owing to rapid advances in nanotechnology, nanomaterials have attracted particular attention to enhance the anticancer efficacy of radiotherapy ( 158 , 161 , 222 , 223 ). Nanoparticle delivery enhances tumor targeting while simultaneously improving effectiveness of radiotherapy by increasing local deposition of ionizing radiation dose or by augmenting production of ROS, DNA damage and cell cycle arrest ( 224 ).…”

“…In additional studies, silver nanoparticles surface modified with polyethyleneglycol (PEG) and aptamer improved nanoparticle penetration and targeting in 3D glioma models, and conjugation with PEG/aptamer further enhanced radiosensitization in C6 xenograft models as well ( 158 ). The development of theragnostics further expand the scope of nanoparticles for multifunctional use ( 161 ). For instance, PEG conjugated bismuth gadolinium oxide nanoparticles (BiGdO3) not only sensitized breast cancer MCF-7 and 4T1 lines and 4T1 xenograft models to radiation, but the bismuth and gadolinium also allowed for MRI and CT imaging ( 161 ).…”