Quantum Dot-labeled Tags Improve Minimal Detection Limit of CA125 in Ovarian Cancer Cells and Tissues

  • Sorour Shojaeian Department of Biochemistry, Medical Genetics, Nutrition, Alborz University of Medical Sciences, Karaj, Iran
  • Abdolamir Allameh Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • Mahmood Jeddi-Tehrani Department of Hybridoma, Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
  • Roya Ghods Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran AND Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medicine Sciences, Tehran, Iran
  • Jaleh Shojaeian University of Maryland School of Pharmacy, Baltimore, Maryland, USA
  • Akram-Sadat Tabatabaei-Panah Department of Biology, Faculty of Basic Sciences, Islamic Azad University, East Tehran Branch (Ghiamdasht), Tehran, Iran
  • Amir-Hassan Zarnani Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran AND Immunology Research Center (IRC), Iran University of Medical Sciences, Tehran, Iran
Keywords: Carcinoma antigen 125, Minimal reactivity limit, Neoplasm micrometastasis, Ovarian neoplasms, Quantum dots, Sensitivity


In recent years, a lot of attention has been paid to quantum dot (QD) nanoparticles as fluorescent sensors for sensitive and accurate detection of cancer biomarkers. Here, using a homemade specific monoclonal antibody against CA125 and QD525- or FITC-labeled probes, expression of this marker in an ovarian cancer cell line and cancer tissues were traced and optical properties of fluorophores were compared qualitatively and quantitatively. Our results clearly showed that besides lower background and exceptionally higher photobleaching resistance, QD525 exhibited higher fluorescent intensity for both ovarian cancer cell and tissues at different exposure times (p<0.0001) and excitation filter sets (p<0.0001) exemplified by significantly higher staining index (p<0.016). More importantly, the FITC-labeled probe detected antigen-antibody complex at minimum concentration of 0.3 mg/mL of anti-CA125, while reactivity limit decreased to 0.078 mg/mL of anti-CA125 when QD525-labeled probe was applied showing four times higher reactivity level of QD525 probe compared to the same probe labeled with FITC. Based on our results, it seems that QDs are inimitable tags for sensitive detection and localization of ovarian cancer micrometastasis and molecular demarcation of cancer tissues in surgical practice, which subsequently figure out accurate therapeutic approaches. 


style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-ascii-theme-font:



field-begin'> ADDIN EN.REFLIST

style='mso-element:field-separator'>1. Das C, Mukhopadhyay M, Ghosh T, Saha AK, Sengupta M. Correlation of Cytohistlogical Expression and Serum Level of Ca125 in Ovarian Neoplasm. Journal of clinical and diagnostic research: JCDR. 2014;8(3):41.

2. Bast Jr RC, Feeney M, Lazarus H, Nadler L, Colvin R, Knapp R. Reactivity of a monoclonal antibody with human ovarian carcinoma. Journal of Clinical Investigation. 1981;68(5):1331.

3. Kabawat S, Bast Jr R, Bhan A, Welch WR, Knapp R, Colvin R. Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125. International Journal of Gynecological Pathology. 1983;2(3):275-85.

4. Wang Z-H, Xu C-J. Research progress of microRNA in early detection of ovarian cancer. Chinese medical journal. 2015;128(24):3363.

5. Hensley ML. A step forward for two-step screening for ovarian cancer. Journal of Clinical Oncology. 2010;28(13):2128-30.

6. Wang L-W, Peng C-W, Chen C, Li Y. Quantum dots-based tissue and in vivo imaging in breast cancer researches: current status and future perspectives. Breast cancer research and treatment. 2015;151(1):7-17.

7. Student M. Quantum Dots for Diagnosis of Cancers. International Journal of Engineering Science. 2017;4691.

8. Zhu Y, Hong H, P Xu Z, Li Z, Cai W. Quantum dot-based nanoprobes for in vivo targeted imaging. Current molecular medicine. 2013;13(10):1549-67.

9. Giepmans BN, Deerinck TJ, Smarr BL, Jones YZ, Ellisman MH. Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots. Nature methods. 2005;2(10):743-9.

10. Costa CR, Feitosa ML, Bezerra DO, Carvalho YK, Olivindo RF, Fernando PB, et al. Labeling of adipose-derived stem cells with quantum dots provides stable and long-term fluorescent signal for ex vivo cell tracking. In Vitro Cellular & Developmental Biology-Animal. 2016:1-8.

11. Deglmann CJ, Blazków-Schmalzbauer K, Moorkamp S, Susha AS, Herrler T, Giunta RE, et al. Cadmium Telluride Quantum Dots as a Fluorescence Marker for Adipose Tissue Grafts. Annals of Plastic Surgery. 2017;78(2):217-22.

12. Shojaeian S, Allameh A, Zarnani AH, Chamankhah M, Ghods R, Bayat AA, et al. Production and characterization of monoclonal antibodies against the extracellular domain of CA 125. Immunological investigations. 2010;39(2):114-31.

13. Shojaeian S, Zarnani AH, Jeddi-Tehrani M, Fereidooni F, Torkabadi E, Akhondi MM, et al. Heterologous Immunization, a Way out of the Problem of Monoclonal Antibody Production against Carcinoma Antigen 125. Iranian Journal of Immunology. 2009;6(4):174.

14. Felder M, Kapur A, Gonzalez-Bosquet J, Horibata S, Heintz J, Albrecht R, et al. MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Molecular cancer. 2014;13(1):129.

15. Mantia-Smaldone GM, Corr B, Chu CS. Immunotherapy in ovarian cancer. Human vaccines & immunotherapeutics. 2012;8(9):1179-91.

16. Waters JC. Accuracy and precision in quantitative fluorescence microscopy. Rockefeller University Press; 2009.

17. Tabatabaei-Panah A-S, Jeddi-Tehrani M, Ghods R, Akhondi M-M, Mojtabavi N, Mahmoudi A-R, et al. Accurate sensitivity of quantum dots for detection of HER2 expression in breast cancer cells and tissues. Journal of fluorescence. 2013;23(2):293-302.

18. Pantel K, Cote RJ, Fodstad Ø. Detection and clinical importance of micrometastatic disease. Journal of the National Cancer Institute. 1999;91(13):1113-24.

19. Alam F, Yadav N. Potential applications of quantum dots in mapping sentinel lymph node and detection of micrometastases in breast carcinoma. Journal of breast cancer. 2013;16(1):1-11.

20. Malik P, Gulia S, Kakkar R. Quantum dots for diagnosis of cancers. Adv Mat Lett. 2013;4:811-22.

21. Abrams B, Dubrovsky T. Quantum dots in flow cytometry. Quantum Dots: Applications in Biology. 2007:185-203.

22. Banks PR, Paquette DM. Comparison of three common amine reactive fluorescent probes used for conjugation to biomolecules by capillary zone electrophoresis. Bioconjugate chemistry. 1994;6(4):447-58.

23. Adams KE, Ke S, Kwon S, Liang F, Fan Z, Lu Y, et al. Comparison of visible and near-infrared wavelength-excitable fluorescent dyes for molecular imaging of cancer. Journal of biomedical optics. 2007;12(2):024017--9.

24. Berlier JE, Rothe A, Buller G, Bradford J, Gray DR, Filanoski BJ, et al. Quantitative comparison of long-wavelength Alexa Fluor dyes to Cy dyes: fluorescence of the dyes and their bioconjugates. Journal of Histochemistry & Cytochemistry. 2003;51(12):1699-712.

25. Gruber HJ, Hahn CD, Kada G, Riener CK, Harms GS, Ahrer W, et al. Anomalous fluorescence enhancement of Cy3 and Cy3. 5 versus anomalous fluorescence loss of Cy5 and Cy7 upon covalent linking to IgG and noncovalent binding to avidin. Bioconjugate chemistry. 2000;11(5):696-704.

26. Hahn CD, Riener CK, Gruber HJ. Labeling of antibodies with Cy3-, Cy3. 5-, Cy5-, and Cy5. 5-monofunctional dyes at defined dye/protein ratios. Single Molecules. 2001;2(2):149-.

27. Hama Y, Urano Y, Koyama Y, Bernardo M, Choyke PL, Kobayashi H. A comparison of the emission efficiency of four common green fluorescence dyes after internalization into cancer cells. Bioconjugate chemistry. 2006;17(6):1426-31.

28. Panchuk-Voloshina N, Haugland RP, Bishop-Stewart J, Bhalgat MK, Millard PJ, Mao F, et al. Alexa dyes, a series of new fluorescent dyes that yield exceptionally bright, photostable conjugates. Journal of Histochemistry & Cytochemistry. 1999;47(9):1179-88.

29. Wang H-Z, Wang H-Y, Liang R-Q, Ruan K-C. Detection of tumor marker CA125 in ovarian carcinoma using quantum dots. Acta Biochimica et Biophysica Sinica. 2004;36(10):681-6.

30. Bruchez M, Moronne M, Gin P, Weiss S, Alivisatos AP. Semiconductor nanocrystals as fluorescent biological labels. Science. 1998;281(5385):2013-6.

31. Chan WC, Nie S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science. 1998;281(5385):2016-8.

font-family:"Times New Roman","serif";mso-ascii-theme-font:major-bidi;




How to Cite
Shojaeian S, Allameh A, Jeddi-Tehrani M, Ghods R, Shojaeian J, Tabatabaei-Panah A-S, Zarnani A-H. Quantum Dot-labeled Tags Improve Minimal Detection Limit of CA125 in Ovarian Cancer Cells and Tissues. Iran J Allergy Asthma Immunol. 17(4):326-335.
Original Article(s)