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Evaluation of the Cell Death Induction of Gold Nanoparticles Conjugated Antibodies Produced Against a Small Epitope of DR5 Protein in MCF7 Cells

Shaghayegh Amirijavid, Maliheh Entezari, Hossein Dehghani





Introduction: Nowadays, versatile and useful features of nanoparticles, especially gold nanoparticles in medicine and healthcare have brought them immense popularity. The ability to transfer towards the special cells, distinguish the different cells and their electrical resonance feature make them as a proper candidate for treatment of cancer. Antibodies which are generated against death receptor, DR5, are powerful tools in the programmed death of cancer cells during induction process. Its association with nanoparticles could efficiently deliver such biological apoptosis inducing drug to the cancer cells


Materials and Methods: In this study, at the first step, gold nanoparticles were produced by chemical methods in the presence of aspartic acid (amino acid). Then, nano-sized ones were selected and subsequently conjugated by mouse antibodies which were produced against a small 21 amino acid peptide from extracellular domain of death receptor, DR5. 


Results: The conjugated antibodies by gold nanoparticles could efficiently kill the MCF7 breast cancer cells through inducing cell death. The combination of antibodies which were generated against a small fragment of the death receptor,


Conclusion:DR, with gold nanoparticles not only minimized the required amount for the purpose of inducing cell death.but also maximizing their efficiency and quality.






Gold nanoparticles , Death receptor, DR5, Mouse antibodies


Amirijavid Sh, Entezari M, Movafagh A, Hashemi M, Mosavi-Jarahi A, Dehghani H. Apoptotic Killing of Breast Cancer Cells by IgYs Produced Against a Small 21 Aminoacid Epitope of the Human TRAIL-2 Receptor. Asian Pacific Journal of Cancer Prevention 2016;17 :293-297.

Nagasaki Y, Kobayashi H, Katsuyama Y, Jomura T, Sakura T. Enhanced immunoresponse of antibody mixed-PEG coimmobilized surface construction of high performance immunomagnetic ELISA system. J Colloid Interface Sci 2007; 309(2):524–530.

Baio G, Fabbi M, d.Totero D, Ferrini S, Cilli M, Derchi LE, Neumaier CE. Magnetic resonance imaging at 1.5T with immunospecific contrast agent in vitro and in vivo in a xeno-transplant model. Mag Reson Mater Phy 2006; 19:313–320.

Itoa A, Kugaa Y, Hondaa H, Kikkawab H, Horiuchib A, Watanabeb Y, et al. Magnetite nanoparticle-loaded anti-her2 immunoliposomes for combination of antibody therapy with hyper-thermia. Cancer Lett 2004; 212(2):167–175.

Kawasaki ES, Player A. Nanotechnology, nano-medicine, and the development of new, effective therapies for cancer. Nanomedicine 2005; 1(2):101–109.

Couvreur P, Vauthier C. Nanotechnology: Intelligent design to treat complex disease. harm. Res 2006; 23:1417–1450.

Alonso MJ. Nanomedicines for overcoming biological barriers. Biomed. Pharmacother 2004; 58:168–172.

Hashemi M, Amirijavid S, Entezari M, Shafaroodi H, Jokar Saghafi Z. Generation and characterization of chicken egg yolk antibodies (IgY) against TNFR1. Bratisl Lek Listy 2015; 116 (5);316-320.

Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2007; 2(12):751-60.

Amirijavid Sh,Hashemi M. Detection of Anticancer and Apoptotic Effect of the Produced IgYs against the Three Extracellular Domain of Human DR5 Protein.Iranian Journal of Cancer Preventation. 2015; 8 (2): 109-115.

Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov 2005; 4:145–160.

Amirijavid Sh, Hashemi M, Akbarzadeh A, Parivar K, Khakpoor M. Anticancer effect of the IgY that produced against a small peptide with 15 amino acids of human DR5 on MCF7 cell line Journal of Paramedical Sciences. 2014; 5(1):2-6 .

Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, et al. TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 1997; 16:5386-5397.

Gura T. How TRAIL kills cancer cells but not normal cells. Sciece 1997; 277(5327):768.

Takeda K, Yamaguchi N, Akiba H, Kojima Y, Hayakawa Y, Tanner JE, et al. Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy. J Exp Med 2004; 199(4):437-48.

Kelley SK, Harris LA, Xie D, Deforge L, Totpal K, BussiereJ, et al. Preclinical Studies to Predict the Disposition of Apo2L/Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Humans: Characterization of in Vivo Efficacy, Pharmacokinetics and Safety.JPET 2001; 299(1):31–38.

Pitti RM, Marsters AS , Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 1996; 271(22):12687-90.

Taieb J, Chaput N, Ménard C, Apetoh L, Ullrich E, Bonmort M, et al. A novel dendritic cell subset involved in tumor immunosurveillance Nature Medicine 2006; 12:214 – 219.

Ichikawa K, Liu W, Zhao L, Wang ZH, Liu D, Ohtsuka T, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity.Nature Medicine 2001; 7:954 – 960.

Humphreys RC, Halpern W. Trail receptors: targets for therapy. AdvExp Med Biol 2008; 615:127-58.

Adams C, Totpal K, Lawrence D, Marsters S, Pitti R, Yee S, et al. Structural and functional analysis of the interaction between the agonistic monoclonal antibody Apomab and the proapoptotic receptor DR5. Cell Death Differ 2008; 15:751–61.

FarahnakZarabi M, Farhangi A, KhademiMazdeh S, Ansarian Z, Zare D, Mehrabi MR, et al. Synthesis of Gold Nanoparticles Coated with Aspartic Acid and Their Conjugation with FVIII Protein and FVIII Antibody. Indian Journal of Clinical Biochemistry 2014; 29:154-160.

Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L. Death Receptor 5, a New Member of the TNFR Family, and DR4 Induce FADD-Dependent Apoptosis and Activate the NF-κBPathway .Immunity 1997; 7(6): 821-830.

Sheridan JP, Marsters SA, Pitti RM. Control of TRAIL-induced apoptosis y a family of signaling and decoy. Sceience 1997; 271:818-21.

Wu GS, Burns TF, McDonald ER, Jiang W, Meng R, Krantz ID, et al. KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor genes. Nat Genet 1997; 17:141-3.

Osoren N, Wafik S, El-Deiry. Cell surface death receptor signaling in norma and cancer cells. Seminars in Cancer Biology 2003; 13(2): 135-147.

Kelly RF, Totpal K, Linds SH, Mathieu M, Billeci K, Deforge L, et al. Receptor selective mutants of apoptos-inducing ligand. J Biol Chem 2005; 280(3): 2205-12.

Almasan A, Ashkenazi A. Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy.Cytokine & Growth Factor Reviews 2003; 1:337-348.

Ichikawa K, Liu W, Zhao L, Wang Z, Liu D, Ohtsuka T, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 2001; 7: 954-960.

Van Holde KE, Miller KI. Hemocyanins. Adv. Protein Chem 1995; 47:1–81.

Harris JR, Markl J. Keyhole limpet hemocyanin (KLH): a biomedical review. Micron 1999; 30: 597–623.

Harris JR, Markl J. Keyhole limpet hemocyanin: molecular structure of a potent marine immunoactivator. A review. Eur. Urol 2000; 37: 24–33.

Feng C, Wang T, Tang R, et al. Silencing of the MYCN gene by siRNA delivered by folate receptor-targeted liposomes in LA-N-5 cells. Pediatr. Surg. Int 2010; 26:1185–1191.

Chen J, Wu H, Han D, et al. Using anti-VEGF McAb and magnetic nanoparticles as double-targeting vector for the radioimmunotherapy of liver cancer. Cancer Lett 2006; 231:169–175.

Skotland T, Iversen TG, Sandvig K. New metal-basednanoparticles for intravenous use: requirements for clinical success with focus on medical imaging. Nanomedicine 2010; 6:730–737.

McCarron PA, Marouf WM, Donnelly RF, et al. Enhanced surface attachment of protein-type targeting ligands to poly(lactide-co-glycolide) nanoparticles using variable expression of polymeric acid functionality. J. Biomed. Mater. Res 2008; 87(4):873–884.

Sorokin P. Mylotarg approved for patients with CD33 acute myeloid leukemia. Clin. J. Oncol. Nurs 2000; 4: 279–280.

Amirijavid S, Entezari M. Comparison of the effects of three kinds of IgYs, (normal, nanoliposomal and nanoparticle conjugated), which are produced against the small domains of DR5 protein on cancer cells. IET Nanobiotechnol. 2018 Jun;12(4):436-440.

Salcedo TW, Alderson RF, Basu S, Beatty S, Choi GH, Corcoran M, et al. TRM-1, a fully human TRAIL-R1 agonistic monoclonal antibody, displays in vitro and in vivo anti-tumor activity. Proceedings of the American Association for Cancer Research 2002; 43:856.

Chen KF, Chen HL, Liu CY, Tai WT, Ichikawa K, Chen PJ, et al. Dovitinibsencitizes hepatocellular carcinoma cells to TRAIL and tigatuzumab, a novel anti-DR5 antibody, through SHP-1-dependent inhibition of STAT3. BiochemPharmacol 2012; 83(6):769-77.

Guo Y, Chen C, Zheng Y, Zhang J, Tao X, Liu S, et al. A novel anti-human DR5 monoclonal antibody with tumoricidal activity induces caspase-dependent and caspase-independent cell death 2005:280(51): 41940-52.

Xiang H, Reyes AE, Eppler S, Kelley S, Damico-Beyer LA. Death receptor 5 agonistic antibody PRO95780: preclinical pharmacokinetics and concentration–effect relationship support clinical dose and regimen selection. Cancer Chemotherapy and Pharmacology 2013; 1-11.

Du YW, Chen JG, Bai HL, Huang HY, Wang J, Li SL, et al. A novel agonistic anti-human death receptor 5 monoclonal antibody with tumoricidal activity induces caspase- and mitochondrial-dependent apoptosis in human leukemia Jurkat cells. Cancer BiotherRadiopharm 2011;26(2):143-52.

DOI: https://doi.org/10.22037/aab.v10i3.26863


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