About 50% of cancer patients receive radiation therapy. Despite the therapeutic benefits of this method, the toxicity of radiation in the normal tissues is unavoidable To improve the quality of radiation therapy, in addition to other methods such as IMRT, IGRT, and high radiation dose, nanoparticles have shown excellent potential when ionising radiation is applied to the target volume. Recently, bismuth-based nanoparticles (BiNPs) have become particularly popular in radiation therapy due to their high atomic numbers (Z), high X-ray attenuation coefficient, low toxicity, and low cost. Moreover, it is easy to synthesise in a variety of sizes and shapes. This study aimed to review the effects of the bismuth-based NP and its combination with other compounds, and their potential synergies in radiotherapy, discussed based on their physical, chemical, and biological interactions. Targeted and non-targeted bismuth-based NPs used in radiotherapy as radiosensitizers and dose enhancement effects are described. The results reported in the literature were categorised into various groups. Also, this review has highlighted the importance of bismuth-based NPs in different forms of cancer treatment to find the highest efficiency for applying them as a suitable candidate for various cancer therapy and future clinical applications. K E Y W O R D S nanomedicine, nanoparticles, radiation therapy | INTRODUCTIONCancer is one of the important leading causes of death worldwide. By 2030, it is estimated that there will be approximately 22 million new cases of cancer worldwide and 13 million deaths from cancer [1,2]. Clinically, the most common cancer treatments include surgery, chemotherapy, and radiation therapy, which are the main non-invasive treatments for many of these types [3]. For this purpose, radiotherapy uses ionising radiation, but unfortunately, due to hypoxia, tumour cells are more resistant to radiation than normal cells. This can lead to treatment failure and can also cause side effects in normal tissues [4]. Hence, the use of radiosensitizers may be beneficial to enhance the delivery of radiation doses to tumour cells [5].Recently, as a new radiosensitising technique in medicine, nanoparticles (NPs) may have improved the treatment of various types of tumours [6]. Therefore, many studies are limited to in vitro and in vivo conditions of nanoparticle application in radiotherapy [7,8]. However, the selection of NPs as radiosensitizers is difficult. Bismuth nanoparticles (BiNPs) with specific properties such as high atomic numbers (Z), high X-ray attenuation coefficient, low toxicity, and low cost can be used as radiosensitizers to increase uptake by many cancer cells and increase absorption of radiation in synergistic cancer therapy [9]. It is also important to note that bismuthThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The aim of this study was to assess the radiosensitivity of bismuth sulfide nanoparticles conjugated with a synthetic agonist analog of gonadotropin-releasing hormones in targeted radiotherapy for breast cancer. After synthesis and characterization of nanoparticles, cytotoxicity of nanoparticles was measured by MTT assay, and the survival fraction was determined by colony formation assay. Finally, flow cytometry was performed to identify the mechanism of radiosensitization. Characterization results determined the spherical shape of Bi2S3@BSA with an average size of 8.649 ± 1.6 nm, and Fourier transform infrared confirmed the successful binding of triptorelin to the surface of the nanoparticles. MTT test results show that the Bi2S3@BSA–triptorelin did not cause any toxicity ( P < 0.05 ) even up to 75 μg/ml. At all doses of ionizing radiation, colony formation assays showed that the nontoxic concentration of Bi2S3@BSA–triptorelin significantly increased cell death in MCF-7 cells compared to Bi2S3@BSA ( P < 0.05 ). The apoptosis test also confirmed colony formation assay results at all doses and introduced apoptosis as a mechanism of radiosensitivity produced by nanoparticles. Certainly, targeted bismuth sulfide nanoparticles can be a good candidate for increasing radiosensitivity against tumor cells.