Modified Bismuth Nanoparticles: A New Targeted Nanoprobe for Computed Tomography Imaging of Cancer

Mohammadi, Milad; Khademi, Sara; Choghazrdi, Yazdan; Irajirad, Rasoul; Keshtkar, Mohammad; Montazerabadi, Alireza

doi:10.22074/cellj.2022.8348

Modified Bismuth Nanoparticles: A New Targeted Nanoprobe for Computed Tomography Imaging of Cancer

Document Type : Original Article

Authors

¹ Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

² Department of Radiology Technology, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran

³ Department of Medical Physics, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

⁴ Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

⁵ Medical Physics and Radiology Department, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

10.22074/cellj.2022.8348

Abstract

Objective: Recently, development of multifunctional contrast agent for effective targeted molecular computed
tomography (CT) imaging of cancer cells stays a major problem. In this study, we explain the ability of Triptorelin
peptide-targeted multifunctional bismuth nanoparticles (Bi2S3@ BSA-Triptorelin NPs) for molecular CT imaging.
Materials and Methods: In this experimental study, the formed nanocomplex of Bi2S3@ BSA-Triptorelin NPs
was characterized using different methods. The MTT cytotoxicity test was performed to determine the appropriate
concentration of nanoparticles in the MCF-7 cells. The X-ray attenuation intensity and Contrast to Noise Ratio (CNR) of
targeted and non-targeted nanoparticles were measured at the concentrations of 25, 50, and 75 μg/ml and X-ray tube
voltages of 90, 120 and 140 kVp.
Results: We showed that the formed Bi2S3@ BSA-Triptorelin NPs with a Bi core size of approximately ~8.6 nm are nontoxic
in a given concentration (0-200 μg/ml). At 90, 120, and 140 tube potentials (kVp), the X-ray attenuation of targeted cells were
1.35, 1.36, and 1.33-times, respectively, more than non-targeted MCF-7cells at the concentration of 75 μg/ml. The CNR
values at 90, 120, and 140 kVp tube potentials were 171.5, 153.8 and 146.3 c/ϭ, respectively.
Conclusion: These ﬁndings propose that the diagnostic nanocomplex of Bi2S3@ BSA-Triptorelin NPs can be applied
as a good contrast medium for molecular CT techniques.

Keywords

20.1001.1.22285806.2022.24.9.4.5

References

1. MacRitchie N, Frleta-Gilchrist M, Sugiyama A, Lawton T, McInnes IB, Maffia P. Molecular imaging of inflammation-Current and emerging technologies for diagnosis and treatment. Pharmacol Ther. 2020; 211: 107550.
2. Cole LE, Ross RD, Tilley JM, Vargo-Gogola T, Roeder RK. Gold nanoparticles as contrast agents in x-ray imaging and computed tomography. Nanomedicine. 2015; 10(2): 321-341.
3. Goldman W. Principles of CT: radiation dose and image quality. J Nucl Med Technol. 2007; 35(4): 213-225.
4. Khademi S, Sarkar S, Shakeri-Zadeh A, Attaran N, Kharrazi S, Ay MR, et al. Folic acid-cysteamine modified gold nanoparticle as a nanoprobe for targeted computed tomography imaging of cancer cells. Mater Sci Eng C Mater Biol Appl. 2018; 89: 182-193.
5. Zhou D, Li C, He M, Ma M, Li P, Gong Y, et al. Folate-targeted perfluorohexane nanoparticles carrying bismuth sulfide for use in US/CT dual-mode imaging and synergistic high-intensity focused ultrasound ablation of cervical cancer. J Mater Chem B. 2016; 4(23): 4164-4181.
6. Zhu HL, Cheng QY, Liao MY, Zhang ZL, Cai WG, Ma JJ, et al. Economical synthesis of ultra-small Bi2S3 nanoparticles for highsensitive CT imaging. Mater Res Express. 2019; 6(9): 095005.
7. Koç MM, Aslan N, Kao AP, Barber AH. Evaluation of X-ray tomography contrast agents: a review of production, protocols, and biological applications. Microsc Res Tech. 2019; 82(6): 812-848.
8. Zheng X, Shi J, Bu Y, Tian G, Zhang X, Yin W, et al. Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non-invasive visualization of the gastrointestinal tract. Nanoscale. 2015; 7(29): 12581-12591.
9. Luo S, Zhang E, Su Y, Cheng T, Shi C. A review of NIR dyes in cancer targeting and imaging. Biomaterials. 2011; 32(29): 7127-7138.
10. Chen ZY, Wang YX, Lin Y, Zhang JS, Yang F, Zhou QL, et al. Advance of molecular imaging technology and targeted imaging agent in imaging and therapy. Biomed Res Int. 2014; 2014: 819324.
11. James ML, Gambhir SS. A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012; 92(2): 897-965.
12. Huerta-Reyes M, Maya-Núñez G, Pérez-Solis MA, López-Muñoz E, Guillén N, Olivo-Marin JC, et al. Treatment of breast cancer with gonadotropin-releasing hormone analogs. Front Oncol. 2019; 9: 943.
13. Deng X, Qiu Q, Ma K, Huang W, Qian H. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormoneconjugated peptide. Amino Acids. 2015; 47(11): 2359-2366.
14. Schally AV, Engel JB, Emons G, Block NL, Pinski J. Use of analogs of peptide hormones conjugated to cytotoxic radicals for chemotherapy targeted to receptors on tumors. Curr Drug Deliv. 2011; 8(1): 11-25.
15. Schally AV, Comaru-Schally AM, Nagy A, Kovacs M, Szepeshazi K, Plonowski A, et al. Hypothalamic hormones and cancer. Front Neuroendocrinol. 2001; 22(4): 248-291.
16. Schally AV, Nagy A. Chemotherapy targeted to cancers through tumoral hormone receptors. Trends Endocrinol Metab. 2004; 15(7): 300-310.
17. Roy J, Kaake M, Low PS. Small molecule targeted NIR dye conjugate for imaging LHRH receptor positive cancers. Oncotarget. 2019; 10(2): 152.
18. Venturelli M, Guaitoli G, Omarini C, Moscetti L. Spotlight on triptorelin in the treatment of premenopausal women with early-stage breast cancer. Breast Cancer (Dove Med Press). 2018; 10: 39-49.
19. Mező G, Manea M. Receptor-mediated tumor targeting based on peptide hormones. Expert Opin Drug Deliv. 2010; 7(1): 79-96.
20. Zu Y, Yong Y, Zhang X, Yu J, Dong X, Yin W, et al. Protein-directed synthesis of Bi2S3 nanoparticles as an efficient contrast agent for visualizing the gastrointestinal tract. RSC Adv. 2017; 7(28): 17505-17513.
21. Vattikuti SVP, Police AKR, Shim J, Byon C. Sacrificial-templatefree synthesis of core-shell C@ Bi2S3 heterostructures for efficient supercapacitor and H2 production applications. Sci Rep. 2018; 8: 4194.
22. De La Vega JC, Häfeli UO. Utilization of nanoparticles as X-ray contrast agents for diagnostic imaging applications. Contrast Media Mol Imaging. 2015; 10(2): 81-95.
23. Ahamed M, Akhtar MJ, Khan MM, Alrokayan SA, Alhadlaq HA. Oxidative stress mediated cytotoxicity and apoptosis response of bismuth oxide (Bi2O3) nanoparticles in human breast cancer (MCF-7) cells. Chemosphere. 2019; 216: 823-831.
24. Dong L, Zhang P, Liu X, Deng R, Du K, Feng J, et al. Renal clearable Bi–Bi2S3 heterostructure nanoparticles for targeting cancer theranostics. ACS Appl Mater Interfaces. 2019; 11(8): 7774-7781.
25. Algethami M, Blencowe A, Feltis B, Geso M. Bismuth sulfide nanoparticles as a complement to traditional iodinated contrast agents at various x-ray computed tomography tube potentials. J Nanomater Mol Nanotechnol. 2017; 9: 25-28.