Aptamer AS1411-functionalized gold nanoparticle-melittin complex for targeting MCF-7 breast cancer cell line

Document Type : Research Paper

Authors

1 Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

6 Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

Abstract

Objective(s): Several studies reported the apoptotic and lytic activity of melittin (Mel) in different tumor cells. In this study, a novel nano-complex was developed composed of AS1411aptamers, melittin and gold nanoparticle for the treatment of breast cancer cells. 
Materials and Methods: Gold nanoparticles (GNP) were synthesized using reduction of tetrachloroauric acid (HAuCl4). Melittin modified with cysteine and AS1411aptamer conjugated to the gold nanoparticle. Gel retardation assay was used to prove the formation of GNP-Mel-AS1411 complex. Physicochemical properties of complex were investigated by Dynamic Light Scattering (DLS). The cytotoxicity of Mel and GNP-Mel-AS1411 complex were evaluated in both MCF‐7 (target) and L929 (non-target) cells by the MTT assay. 
Results: The average size of GNP and GNP-Mel-AS1411 complex were 20 ± 2.5 and 270.5± 3.2 respectively. The results of MTT assay revealed that this nanocomplex was more cytotoxic in MCF‐7 (cell viability = 19% ± 2%) and less cytotoxic in L929 cells (cell viability = 73% ± 1.6%).
Conclusion: The results of this study indicated that the gold nanoparticle-melittin-AS1411 complex had a potential value in cancer cell targeted delivery of melittin. 

Keywords


1.    Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. 2021;71(3):209-249.
2.    Tanaka T, Decuzzi P, Cristofanilli M, Sakamoto JH, Tasciotti E, Robertson FM, et al. Nanotechnology for breast cancer therapy. Biomed Microdevices. 2009;11(1):49-63.
3.    Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. NEJM. 2001;344(26):1997-2008.
4.    Samadian H, Hosseini-Nami S, Kamrava SK, Ghaznavi H, Shakeri-Zadeh A. Folate-conjugated gold nanoparticle as a new nanoplatform for targeted cancer therapy. J Cancer Res Clin Oncol. 2016;142(11):2217-2229.
5.    Jeong EH, Jung G, Hong CA, Lee H. Gold nanoparticle (AuNP)-based drug delivery and molecular imaging for biomedical applications. Archives of pharmacal research. 2014;37(1):53-59.
6.    Kim D-H, Seo J-M, Shin K-J, Yang S-G. Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy. Biomater Res. 2021;25(1):1-12.
7.    Bates PJ, Reyes-Reyes EM, Malik MT, Murphy EM, O’toole MG, Trent JO. G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms. Biochim Biophys Acta. 2017;1861(5):1414-1428.
8.    Sader M, Courty J, Destouches D. Nanoparticles functionalized with ligands of cell surface nucleolin for cancer therapy and diagnosis. J Nanomed Nanotechnol. 2015;6(310):2.
9.    Soundararajan S, Chen W, Spicer EK, Courtenay-Luck N, Fernandes DJ. The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer res. 2008;68(7):2358-2365.
10.    Girvan AC, Teng Y, Casson LK, Thomas SD, Jüliger S, Ball MW, et al. AGRO100 inhibits activation of nuclear factor-κB (NF-κB) by forming a complex with NF-κB essential modulator (NEMO) and nucleolin. Mol Cancer Ther. 2006;5(7):1790-1799.
11.    Pichiorri F, Palmieri D, De Luca L, Consiglio J, You J, Rocci A, et al. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation. J Exp Med. 2013;210(5):951-968.
12.    Van Den Bogaart G, Guzmán JV, Mika JT, Poolman B. On the mechanism of pore formation by melittin. J Biol Chem. 2008;283(49):33854-33857.
13.    Zhou J, Wan C, Cheng J, Huang H, Lovell JF, Jin H. Delivery strategies for melittin-based cancer therapy. ACS Appl Mater Interfaces. 2021;13(15):17158-173.
14.    Turkevich J, Stevenson PC, Hillier J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Faraday Discuss. 1951;11:55-75.
15.    Shahdordizadeh M, Yazdian-Robati R, Ansari N, Ramezani M, Abnous K, Taghdisi SM. An aptamer-based colorimetric lead (II) assay based on the use of gold nanoparticles modified with dsDNA and exonuclease I. MCA. 2018;185(2):1-6.
16.    Dam DHM, Lee JH, Sisco PN, Co DT, Zhang M, Wasielewski MR, et al. Direct observation of nanoparticle–cancer cell nucleus interactions. ACS nano. 2012;6(4):3318-3326.
17.    Abnous K, Danesh NM, Ramezani M, Lavaee P, Jalalian SH, Yazdian-Robati R, et al. A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells. RSC adv. 2017;7(25):15181-15188.
18.    Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp Mol Pathol. 2009151-164.
19.    Kong T, Zhou R, Zhang Y, Hao L, Cai X, Zhu B. AS1411 aptamer modified carbon dots via polyethylenimine‐assisted strategy for efficient targeted cancer cell imaging. Cell Prolif. 2020;53(1):e12713.
20.    Rajabnejad SH, Mokhtarzadeh A, Abnous K, Taghdisi SM, Ramezani M, Razavi BM. Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer. Drug Dev Ind Pharm. 2018;44(6):982-987.
21.    Mansouri M, Moallem SA, Asili J, Etemad L. Cytotoxic and apoptotic effects of scrophularia umbrosa dumort extract on MCF-7 breast cancer and 3T3 cells. Rep Biochem Mol Biol. 2019;8(1):79.
22.    Raghuraman H, Chattopadhyay A. Melittin: a membrane-active peptide with diverse functions. Biosci Rep. 2007;27(4-5):189-223.
23.    Yazdian-Robati R, Arab A, Ramezani M, Rafatpanah H, Bahreyni A, Nabavinia MS, et al. Smart aptamer-modified calcium carbonate nanoparticles for controlled release and targeted delivery of epirubicin and melittin into cancer cells in vitro and in vivo. Drug Dev Ind Pharm. 2019;45(4):603-610.
24.    Ramazi S, Zahiri J. Posttranslational modifications in proteins: resources, tools and prediction methods. Database. 2021;2021.
25.    Malik MT, O’Toole MG, Casson LK, Thomas SD, Bardi GT, Reyes-Reyes EM, et al. AS1411-conjugated gold nanospheres and their potential for breast cancer therapy. Oncotarget. 2015;6(26):22270.
26.    Zhang F, Correia A, Mäkilä E, Li W, Salonen J, Hirvonen JJ, et al. Receptor-mediated surface charge inversion platform based on porous silicon nanoparticles for efficient cancer cell recognition and combination therapy. ACS Appl Mater Interfaces. 2017;9(11):10034-10046.
27.    Misra SK, Ye M, Kim S, Pan D. Defined nanoscale chemistry influences delivery of peptido-toxins for cancer therapy. PLoS One. 2015;10(6):e0125908.
28.    Russell PJ, Hewish D, Carter T, Sterling-Levis K, Ow K, Hattarki M, et al. Cytotoxic properties of immunoconjugates containing melittin-like peptide 101 against prostate cancer: in vitro and in vivo studies. Cancer Immunol Immunother. 2004;53(5):411-421.
29.    Van der Ven CF, Tibbitt MW, Conde J, Van Mil A, Hjortnaes J, Doevendans PA, et al. Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel. Nanoscale. 2021;13(48):20451-20461.
30.    Ajnai G, Chiu A, Kan T, Cheng C-C, Tsai T-H, Chang J. Trends of gold nanoparticle-based drug delivery system in cancer therapy. J Exp Clin Med. 2014;6172-178.