Targeted detection of the cancer cells using the anti-CD24 bio modified PEGylated gold nanoparticles: the application of CD24 as a vital cancer biomarker

Document Type : Research Paper


1 Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

3 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

4 Department of Radiology, Paramedical School, Tabriz University of Medical Sciences, Tabriz, Iran


Objective(s): The central role of molecular imaging modalities in cancer management is an undeniable fact that could help to diagnose cancer tumors in early stages. The main aim of this study is to prepare a novel targeted molecular imaging nanoprobe of CD24-PEGylated Au NPs to improve the ability of Computed tomography scanning (CT scan) outputs for both in vitro and in vivo detection of breast cancer (4T1) cells.
Materials and methods: Gold nanoparticles (Au NPs) were synthesized and coated with polyethylene glycol (PEG) chains in order to improve the stability of the Au NPs and to provide bio modification points for antibody immobilization. The synthesized nanoprobe was used for both in vitro and in vivo targeted CT imaging breast cancer cells (4T1) and the xenograft tumor model.
Results: Findings showed that the attenuation coefficient of 4T1 cells that were targeted by CD24-PEGylated Au NPs is calculated to be over two times higher than the untargeted 4T1 cells (15 HU vs 39 HU, respectively). Indeed, the results clearly reveal that the developed CD24-PEGylated Au NPs showed the tumor CT enhancement was higher than that of Omnipaqe which used as control.
Also, the CT number values of the tumor area at different time points gradually increased after 60 min post injection and was significantly higher than before injection.
Conclusions: Results showed the introduced CT imaging nanoprobe (Au NPs-PEGylated) could be useful for CT imaging of breast tumors under in vivo condition. Overall, it is concluded that Au NPs-PEGylated contrast media is able to detect breast cancer (4T1) cells and is more effective compared with other casual methods.


1.Bernstein, A. L.; Dhanantwari, A.; Jurcova, M.; Cheheltani, R.; Naha, P. C.; Ivanc, T.; Shefer, E.; Cormode, D. P., Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods. Sci Rep. 2016; 17: 6: 26177.
2.Nanni, C.; Rubello, D.; Fanti, S.; Farsad, M.; Ambrosini, V.; Rampin, L.; Banti, E.; Carpi, A.; Muzzio, P.; Franchi, R., Role of 18F-FDG-PET and PET/CT imaging in thyroid cancer. Biomed Pharmacothe. 2006; 60 (8): 409-413.
3.Herschman, H. R., Molecular imaging: looking at problems, seeing solutions. Science. 2003; 302 (5645), 605-608.
4.Hussain, T.; Nguyen, Q. T., Molecular imaging for cancer diagnosis and surgery. Adv Drug Deliv Rev. 2014; 66, 90-100.
5.Moradi Khaniabadi P, D. Shahbazi-Gahrouei,  M. Suhaimi Jaafar, M. A. A. Majid Shah, B. Moradi Khaniabadi, S. Shahbazi-Gahrouei. Magnetic iron oxide nanoparticles as T2 MR imaging contrast agent for detection of breast cancer (MCF-7) cell. Avicenna J Med Biotechnol. 2017; 9(4): 181-188.
6.James, M. L.; Gambhir, S. S., A molecular imaging primer: modalities, imaging agents, and applications. Physiol Rev. 2012; 92(2): 897-965.
7.Kircher, M. F.; Willmann, J. K., Molecular body imaging: MR imaging, CT, and US. Part I. Principles. Radiology. 2012; 263(3): 633-643.
8.Hyafil, F.; Cornily, J.-C.; Feig, J. E.; Gordon, R.; Vucic, E.; Amirbekian, V.; Fisher, E. A.; Fuster, V.; Feldman, L. J.; Fayad, Z. A., Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat Med. 2007; 13(5): 636-641.
9.Liu, H.; Xu, Y.; Wen, S.; Chen, Q.; Zheng, L.; Shen, M.; Zhao, J.; Zhang, G.; Shi, X., Targeted tumor computed tomography imaging using low‐generation dendrimer‐stabilized gold nanoparticles. Chem-Eur J. 2013; 19 (20): 6409-6416.
10.Sharifian, S.; Shahbazi-Gahrouei, D. Dose Assessment in multidetector computed tomography (CT) of polymethylmethacrylate (PMMA) phantom using American Association of Physicists in Medicine-Task Group Report No. 111 (AAPM-TG111). J Isfahan Med Sch. 2017; 35(421): 200-205.
11.Wang, H.; Zheng, L.; Peng, C.; Shen, M.; Shi, X.; Zhang, G., Folic acid-modified dendrimer-entrapped gold nanoparticles as nanoprobes for targeted CT imaging of human lung adencarcinoma. Biomaterials. 2013; 34 (2): 470-480.
12.Keshtkar M.; Shahbazi-Gahrouei D.; Khoshfetrat S. M.; Mehrgardi, M. A.; Aghaei M. Aptamer-conjugated magnetic nanoparticles as targeted magnetic resonance imaging contrast agent for breast cancer. J Med Sign Sens. 2016; 6(4): 243-247.
13.Li, Y.; Qi, X.; Lei, C.; Yue, Q.; Zhang, S., Simultaneous SERS detection and imaging of two biomarkers on the cancer cell surface by self-assembly of branched DNA-gold nanoaggregates. Chem Commun (Camb)2014; 50(69): 9907-9909.
14.Ai, K.; Liu, Y.; Liu, J.; Yuan, Q.; He, Y.; Lu, L., Large-scale synthesis of Bi(2)S(3) nanodots as a contrast agent for in vivo X-ray computed tomography imaging. Adv Mater. 2011; 23(42): 4886-4891.
15.Gratton, S. E.; Ropp, P. A.; Pohlhaus, P. D.; Luft, J. C.; Madden, V. J.; Napier, M. E.; DeSimone, J. M., The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U. S. A.  2008; 105(33): 11613-11618.
16.Huang, X.; Teng, X.; Chen, D.; Tang, F.; He, J., The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Biomaterials. 2010; 31(3): 438-448.
17.Ghahremani F, Shahbazi-Gahrouei D, Kefayat A, Motaghi H, Mehrgardi MA, Javanmard SH. AS1411 aptamer conjugated gold nanoclusters as a targeted radiosensitizer for megavoltage radiation therapy of 4T1 breast cancer cells. RSC Adv. 2018; 8: 4249-4258.
18.Lesniak, A.; Fenaroli, F.; Monopoli, M. P.; Aberg, C.; Dawson, K. A.; Salvati, A., Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. ACS nano. 2012; 6(7): 5845-5857.
19.Shang, L.; Nienhaus, K.; Nienhaus, G. U., Engineered nanoparticles interacting with cells: size matters. J Nanobiotechnology. 2014; 12, 5.
20.Wolfram, J.; Yang, Y.; Shen, J.; Moten, A.; Chen, C.; Shen, H.; Ferrari, M.; Zhao, Y., The nano-plasma interface: Implications of the protein corona. Colloids Surf B Biointerfaces. 2014; 124: 17-24.
21.Peng, C.; Li, K.; Cao, X.; Xiao, T.; Hou, W.; Zheng, L.; Guo, R.; Shen, M.; Zhang, G.; Shi, X., Facile formation of dendrimer-stabilized gold nanoparticles modified with diatrizoic acid for enhanced computed tomography imaging applications. Nanoscale. 2012; 4(21): 6768-78.
22.Peng, C.; Zheng, L.; Chen, Q.; Shen, M.; Guo, R.; Wang, H.; Cao, X.; Zhang, G.; Shi, X., PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography. Biomaterials. 2012; 33(4): 1107-1119.
23.Reuveni, T.; Motiei, M.; Romman, Z.; Popovtzer, A.; Popovtzer, R., Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study. Int J Nanomedicine. 2011; 6: 2859-2864.
24.Wang, H.; Zheng, L.; Peng, C.; Guo, R.; Shen, M.; Shi, X.; Zhang, G., Computed tomography imaging of cancer cells using acetylated dendrimer-entrapped gold nanoparticles. Biomaterials. 2011; 32(11): 2979-2988.
25.Acharya, S.; Sahoo, S. K., PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2011; 63(3): 170-183.
26.Aggarwal, P.; Hall, J. B.; McLeland, C. B.; Dobrovolskaia, M. A.; McNeil, S. E., Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliv Rev. ‎ 2009; 61(6): 428-437.
27.Nakagawa, T.; Gonda, K.; Kamei, T.; Cong, L.; Hamada, Y.; Kitamura, N.; Tada, H.; Ishida, T.; Aimiya, T.; Furusawa, N.; Nakano, Y.; Ohuchi, N., X-ray computed tomography imaging of a tumor with high sensitivity using gold nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol chains on their surface. Sci Technol Adv Mater. 2016; 17(1): 387-397.
28.Droz, D.; Zachar, D.; Charbit, L.; Gogusev, J.; Chretein, Y.; Iris, L., Expression of the human nephron differentiation molecules in renal cell carcinomas. Am J Pathol. 1990; 137 (4): 895-905.
29.Eck, W.; Nicholson, A. I.; Zentgraf, H.; Semmler, W.; Bartling, S., Anti-CD4-targeted gold nanoparticles induce specific contrast enhancement of peripheral lymph nodes in X-ray computed tomography of live mice. Nano Lett. 2010; 10 (7): 2318-2322.
30.Kristiansen, G.; Denkert, C.; Schluns, K.; Dahl, E.; Pilarsky, C.; Hauptmann, S., CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol.‎ 2002; 161 (4): 1215-1221.
31.Liu, W.; Vadgama, J. V., Identification and characterization of amino acid starvation-induced CD24 gene in MCF-7 human breast cancer cells. Int J Oncol. 2000; 16(5): 1049-1054.
32.Welsh, J. B.; Zarrinkar, P. P.; Sapinoso, L. M.; Kern, S. G.; Behling, C. A.; Monk, B. J.; Lockhart, D. J.; Burger, R. A.; Hampton, G. M., Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc Natl Acad Sci. U. S. A 2001; 98(3): 1176-1181.
33.Kappelmayer, J.; Nagy, B., Jr., The Interaction of Selectins and PSGL-1 as a Key Component in Thrombus Formation and Cancer Progression. Biomed Res Int. 2017; 6138145.
34.Wang, L.; Liu, Q.; Hu, Z.; Zhang, Y.; Wu, C.; Yang, M.; Wang, P., A novel electrochemical biosensor based on dynamic polymerase-extending hybridization for E. coli O157:H7 DNA detection. Talanta. 2009; 78(3): 647-652.
35.Cai, Q. Y.; Kim, S. H.; Choi, K. S.; Kim, S. Y.; Byun, S. J.; Kim, K. W.; Park, S. H.; Juhng, S. K.; Yoon, K. H., Colloidal gold nanoparticles as a blood-pool contrast agent for X-ray computed tomography in mice. Invest Radiol. 2007; 42(12): 797-806.
36.Lusic, H.; Grinstaff, M. W., X-ray-computed tomography contrast agents. Chem Rev. 2013; 113(3): 1641-1666.
37.L. Adumeau, C. Genevois, L. Roudier, C. Schatz, F. Couillaud, S. Mornet, Impact of surface grafting density of PEG macromolecules on dually fluorescent silica nanoparticles used for the in vivo imaging of subcutaneous tumors, Biochim Biophys Acta. 1861(6) (2017): 1587-1596.
38.D.K. Macharia, Q. Tian, L. Chen, Y. Sun, N. Yu, C. He, H. Wang, Z. Chen, PEGylated (NH4)xWO3 nanorods as efficient and stable multifunctional nanoagents for simultaneous CT imaging and photothermal therapy of tumor, J Photochem Photobiol B. 174 (2017): 10-17.
39.L.E. van Vlerken, T.K. Vyas, M.M. Amiji, Poly(ethylene glycol)-modified nanocarriers for tumor-targeted and intracellular delivery, Pharm Res. 24(8) (2007): 1405-1414.