Novel chitosan-quinic acid nanoparticles labeled with m99 technetium for breast cancer imaging

Document Type : Research Paper


1 Faculty of Pharmacy, Islamic Azad University, Tehran, Iran

2 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

4 Pasteur Institute of Iran


Objective(s): Today, cancer is one of the health concerns in modern societies. The use of nanoparticles in medical science has created new possibilities for diagnosis, imaging of tumors, and treatment of cancer in humans. 
Materials and Methods: In this study, chitosan nanoparticles modified with quinic acid were used to diagnose breast cancer using a single-photon emission computed tomography imaging technique. For this purpose, quinic acid was activated by EDC/NHS and then binding was performed by adding chitosan nanoparticles. 
Results: TEM, DLS, FTIR, and LC/MASS analyzes were used to investigate this conjugation. MTT toxicity test showed no toxicity on the HEK-293 cell lines and therapeutic properties for the MCF-7 cell line. The response surface method depends on the central composite design that was applied. For the highest labeling efficiency, using 3 factors: the amount of chitosan-quinic acid, pH, and SnCl2 as a reducing agent, and the efficiency of labeling was evaluated by thin-layer chromatography (TLC). 
Conclusion: Finally, the study of biodistribution using SPECT imaging in cancer mice and its comparison with blocking tests showed that this compound has a good ability to diagnose breast cancer.


1. Balekouzou A, Yin P, Pamatika CM, Bishwajit G, Nambei SW, Djeintote M, Ouansaba BE, Shu C, Yin M, Fu Z. Epidemiology of breast cancer: retrospective study in the Central African Republic. BMC Public Health. 2016;16(1):1-10. 
2. Rojas K, Stuckey A. Breast cancer epidemiology and risk factors. Clin Obstet Gynecol. 2016;59(4):651-672. 
3. Winters S, Martin C, Murphy D, Shokar NK. Breast cancer epidemiology, prevention, and screening. Prog Mol Biol Transl Sci. 2017;151:1-32. 
4. Nyrop KA, Lee JT, Deal AM, Ki Choi S, Muss HB. Weight-related communications between oncology clinicians and women with obesity at early breast cancer diagnosis: findings from a review of electronic health records. Nutr Cancer. 2020;72(4):576-583. 
5. Hidayat K, Zhou H-J, Shi B-M. Influence of physical activity at a young age and lifetime physical activity on the risks of 3 obesity-related cancers: systematic review and meta-analysis of observational studies. Nutr Rev. 2020;78(1):1- 18. 
6. Sun Q, Xie W, Wang Y, Chong F, Song M, Li T, Xu L, Song C. Alcohol consumption by beverage type and risk of breast cancer: A dose-response meta-analysis of prospective cohort studies. Alcohol Alcohol. 2020;55(3):246- 253. 
7. Orange ST, Hicks KM, Saxton JM. Effectiveness of diet and physical activity interventions amongst adults attending colorectal and breast cancer screening: a systematic review and meta-analysis. CCC. 2021;32(1):13-26. 
8. Kispert S, McHowat J. Recent insights into cigarette smoking as a lifestyle risk factor for breast cancer. Breast Cancer. 2017;9:127. 
9. Sollie M, Bille C. Smoking and mortality in women diagnosed with breast cancer—a systematic review with meta-analysis based on 400,944 breast cancer cases. Gland Surg. 2017;6(4):385. 
10. De Moulin D. A short history of breast cancer: Springer Science & Business Media; 2012. 
11. Colditz GA, Kaphingst KA, Hankinson SE, Rosner B. Family history and risk of breast cancer: Nurses’ health study. Breast Cancer Res Treat. 2012;133(3):1097- 1104. 
12. Abubakar M, Sung H, Devi B, Guida J, Tang TS, Pfeiffer RM, Yang XR. Breast cancer risk factors, survival and recurrence, and tumor molecular subtype: analysis of 3012 women from an indigenous Asian population. Breast Cancer Research. 2018;20(1):1-14. 
13. Group EHBCC. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Journal of the National Cancer Institute. 2003;95(16):1218-1226. 
14. Barsotti Santos D, Ford NJ, Dos Santos MA, Vieira EM. Breast cancer and sexuality: The impacts of breast cancer treatment on the sex lives of women in Brazil. Cult Health Sex. 2014;16(3):46-257. 
15. Johnson HM, Mitchell KB. Breastfeeding and breast cancer: Managing lactation in survivors and women with a new diagnosis. Ann Surg Oncol. 2019;26(10):3032- 3039. 
16. Unar-Munguía M, Torres-Mejia G, Colchero MA, Gonzalez de Cosio T. Breastfeeding mode and risk of breast cancer: a dose–response meta-analysis. J Hum Lact. 2017;33(2):422-434. 
17. Kamińska M, Ciszewski T, Łopacka-Szatan K, Miotła P, Starosławska E. Breast cancer risk factors. Prz Menopauzalny. 2015;14(3):196-202.
18. Hilakivi-Clarke L. Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters. Breast Cancer Research. 2014;16(2):1-10. 
19. Boyd NF, Martin LJ, Bronskill M, Yaffe MJ, Duric N, Minkin S. Breast Tissue Composition and Susceptibility to Breast Cancer. Journal of the National Cancer Institute. 2010; 102(16): 1224-1237. 
20. Kumar M, Salem K, Tevaarwerk AJ, Strigel RM, Fowler AM. Recent advances in imaging steroid hormone receptors in breast cancer. J Nucl Med. 2020;61(2):172-176. 
21. Louie MC, Sevigny MB. Steroid hormone receptors as prognostic markers in breast cancer. Am J Cancer Res. 2017;7(8):1617. 
22. Abdulkareem I. A review on aetio-pathogenesis of breast cancer. J Genet Syndr Gene Ther. 2013;4(142):2. 
23. Holen I, Speirs V, Morrissey B, Blyth K. In vivo models in breast cancer research: progress, challenges and future directions. Dis Model Mech. 2017;10(4):359- 371. 
24. Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res. 2017;50(1): 1-23. 
25. Ali A, Ahmed S. A review on chitosan and its nanocomposites in drug delivery. Int J Biol Macromol. 2018;109:273-286. 
26. Younes I, Rinaudo M. Chitin and chitosan preparation from marine sources. Structure, properties and applications. Mar Drugs. 2015; 13(3): 1133-1174. 
27. Goy RC, BRITTO Dd, Assis OB. A review of the antimicrobial activity of chitosan. Polímeros: Ciência e Tecnologia. 2009;19(3):241-247. 
28. Kean T, Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv Drug Delive Rev. 2010;62(1):3-11. 
29. Hu Y-L, Qi W, Han F, Shao J-Z, Gao J-Q. Toxicity evaluation of biodegradable chitosan nanoparticles using a zebrafish embryo model. Int J Nanomedicine. 2011;6:3351. 
30. Mohammed MA, Syeda J, Wasan KM, Wasan EK. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics. 2017;9(4): 53.
31. Rezaei aghdam H, Bitarafan Rajabi A, Sadat Ebrahimi SE, Beiki D, Abdi K, Mousavi Motlagh SS , Kiani Dehkordi B, Darbandi Azar A, Shafiee Ardestani M. 18F-FDG MicroPET and MRI Targeting Breast Cancer Mouse Model with Designed Synthesis Nanoparticles. J Nanomater. 2022;5737835.