Targeted Intracellular Heat Transfer in Cancer Therapy: Assessment of Asparagine-laminated Gold Nanoparticles in Cell Model of T cell Leukemia

  • Shadab SHAHRIARI Biosensor Research Center, Endocrinology and Metabolism Cellular-Molecular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Maryam BAKHSHI Biosensor Research Center, Endocrinology and Metabolism Cellular-Molecular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Ahmad Reza SHAHVERDI Biotechnology Research Center, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Azar BERAHMEH Dept. of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  • Farnaz SAFAVIFAR Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Mohammad Reza KHORRAMIZADEH Mail Biosensor Research Center, Endocrinology and Metabolism Cellular-Molecular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Gold nanoparticles, Asparagine, Acute lymphoblastic leukemia, CCRF-CEM cells


Background: High temperatures have destructive effects on cancer cells by damaging proteins and structures within cells. Gold nanoparticles (AuNPs) can act as drug delivery vehicles, especially for cancer therapy. Due to the selective intake of asparagine molecules into malignant cells, AuNPs were coated with asparagine; and CCRF-CEM human T-cell leukemia cells were treated with the new combination, Asn-AuNPs, at 39 °C.

Methods: The co-authors from a number of collaborative labs located at Tehran University of Medical Sciences, Tehran, Iran, have initiated the idea and preliminary design of this study in 2011. Hydroxyl surfaced AuNPs were preliminary prepared by tannin free ethanol extract of black tea leaves. These biogenic AuNPs were further capped with asparagines to form asparagine-gold nanoparticle conjugates (Asn-AuNP conjugates). Then CCRF-CEM human T-cell leukemia cells were separately treated with different concentrations of AuNPs and Asn-AuNP conjugates (3, 30, 300 µg/mL). MTT assay and zymography analysis were carried out, and the apoptotic and necrotic effects of Asn-AuNPs were determined in comparison with AuNPs, using flow cytometry assay.

Results: Asn-AuNP conjugates at 300 µg/mL significantly inhibited MMPs at 39 °C, compared to AuNPs. In terms of cytotoxicity, a remarkable decrease was observed in the percentage of viable cells treated with Asn-AuNP conjugates, rather than AuNPs. Moreover, the AuNPs and Asn-AuNP conjugates enhanced the level of apoptosis at almost similar rates.

Conclusion: AuNPs are coated with asparagine molecules and the temperature is slightly increased by 2 °C, the apoptosis is not only enhanced among cells but also shifts to necrosis in higher concentrations of Asn-AuNP conjugates. More investigations should be carried out to explain the exact mechanism underlying the necrotic effects of Asn-AuNPs.




Mieszawska AJ, Mulder WJ, Fayad ZA, Cormode DP (2013). Multifunctional Gold Nanoparticles for Diagnosis and Therapy of Disease. Mol Pharm, 10(3):831–847.

Jain S, Hirst DG, O'Sullivan JM (2012). Gold nanoparticles as novel agents for cancer therapy. Br J Radiol, 85(1010):101-13.

Lia Y, Schluesenerb HJ, Xua S (2010). Gold nanoparticle-based biosensors. Gold Bull, 43(1):29-41.

Anil Kumar1, Huili Ma1, Xu Zhang, Keyang Huang, Shubin Jin, Juan Liu, Xing-Jie Liang (2012). Gold nanoparticles func-tionalized with therapeutic and targeted peptides for cancer treatment. Biomaterials, 33 (4): 1180–9.

Kumar A, Zhang X, Liang XJ (2013). Gold nanoparticles: Emerging paradigm for targeted drug delivery system. Biotechnol Adv, 31 (5): 593–606.

Zhao Y, Jiang X (2013). Multiple strategies to activate gold nanoparticles as antibiot-ics. Nanoscale, 5: 8340-50.

Pooja M Tiwari, Komal Vig, Vida A Dennis, Shree R Singh (2011). Functionalized Gold Nanoparticles and Their Biomedi-cal Applications. Nanomaterials, 1: 31-63.

AK Khan, R Rashid, G Murtaza, A Zahra (2014). Gold Nanoparticles: Synthesis and Applications in Drug Delivery. Trop J Pharm Res,13(7):1169-1177.

Shah NB, Dong J, Bischof JC (2011). Cellu-lar uptake and nanoscale localization of gold nanoparticles in cancer using label-free confocal Raman microscopy. Mol Pharm, 8(1):176-84.

Wolf P (2008). Innovations in biological cancer therapy, a guide for patients and their relatives. NaturaSanitas Germany, pp.:28-57

Baronzio GF, and Hager ED (2010). Hyper-thermia in Cancer Treatment: A Primer. Springer USA, pp.:3-12

Fotopoulou C, Cho CH, Kraetschell R, Gel-lermann J, Wust P, Lichtenegger W, Sehouli J (2010). Regional abdominal hy-perthermia combined with systemic chemotherapy for the treatment of pa-tients with ovarian cancer relapse: Results of a pilot study. Int J Hyperthermia, 26 (2): 118-26.

Hainfeld JF, Dilmanian FA, Zhong Z, Slat-kin DN, Kalef-Ezra JA, Smilowitz HM (2010). Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma. Phys Med Biol, 55(11): 3045-59.

Bona C, Bonilla FA (1996). Textbook of immu-nology. 2nd ed. Boca Raton, FL: CRC Press.

MacEwen EG, Rosenthal RC, Fox LE, Loar AS, Kurzman ID (1992). Evaluation of L-asparaginase: Polyethylene glycol conju-gate versus native L-asparaginase com-bined with chemotherapy: a randomized double-blind study in canine lymphoma. J Vet Intern Med, 6(4): 230-4.

Mukherjee P, Bhattacharya R, Bone N, Lee YK, Patra CR, Wang S, Lu L, Secreto C, et al (2007). Potential therapeutic applica-tion of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL): enhancing apoptosis. J Nanobiotechnology, 5: 4.

Ramezani N, Ehsanfar Z, Shamsa F, Amin GH, Shahverdi HR, Monsef-Esfahani HR, et al (2008). Screening of medicinal plant methanol extracts for the synthesis of gold nanoparticles by their reducing potential. Z Naturforsch B Chem Sci, 63(7): 903-8.

Franco-Romano M, Gil ML, Palacios-Santander JM, Delgado-Jaén JJ (2014). Sonosynthesis of gold nanoparticles from a geranium leaf extract. Ultrason Sonochem, 21(4):1570-7.

Banoee M, Mokhtari N, Akhavan Sepahi A, Jafari Fesharaki P, Monsef-Esfahani HR, Ehsanfar Z, Khoshayand MR, Shahverdi AR (2010). The green synthesis of gold nanoparticles using the ethanol extract of black tea and its tannin free fraction. Iran J Mater Sci Eng, 7(1): 48-53.

Freshney RI (2000). Culture of animal cells; a manual of basic techniques. 2nd ed. New York: Wiley-VCH.

Patricia AM, Beurden S, Von den Hoff JW (2005). Zymographic techniques for the analysis of matrix metalloproteinases and their inhibitors. Biotechniques, 38(1): 73-83.

Mohamed Anwar K Abdelhalim, Mohsen M. Mady and Magdy M. Ghannam (2012). Physical Properties of Different Gold Nanoparticles: Ultraviolet-Visible and Fluorescence Measurements. J Nano-med Nanotechol, 3:133.

Sastry M, Mayya KS, Bandyopadhyay K (1997). pH dependent changes in the op-tical properties of carboxylic acid derivat-ized silver colloidal particles. Colloids Surf A Physicochem Eng Asp, 127(1-3): 221-28.

Singaravelu G, Arockiamary JS, Ganesh Kumarb V, Govindaraju K (2007). A novel extracellular synthesis of monodis-perse gold nanoparticles using marine al-ga. Sargassum wightii Greville. Colloid Surf B Biointerfaces, 57(1): 97-101.

Paino IM, Marangoni VS, de Oliveira Rde C, Antunes LM, Zucolotto V (2012). Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells. Toxicol Lett, 215(2):119-125.

João Conde, Jorge T. Dias, Valeria Grazú, Maria Moros, Pedro V. Baptista, and Je-sus M. de la Fuente (2014). Revisiting 30 years of biofunctionalization and surface chemistry of inorganic nanoparticles for nanomedicine. Front Chem, 2: 48.

RA Sperling, WJ Parak (2010). Surface modi-fication, functionalization and bioconju-gation of colloidal inorganic nanoparti-cles. Phil Trans R Soc A, 368(1915): 1333–1383.

Lin J, Zhang H, Chen Z, Zheng Y (2010). Penetration of lipid membranes by gold nanoparticles: insights into cellular uptake, cytotoxicity, and their relationship. ACS Nano,4(9): 5421-9.

Arya R, Mallik M, Lakhotia SC. (2007). Heat shock genes–integrating cell survival and death. J Biosci, 32(3): 595-610.

Chunyan He, Ann Stroink, Laura Vogel, Chen Xu Wang. (2013) Temperature In-crease Exacerbates Apoptotic Neuronal Death in Chemically-Induced Ischemia. PLoS One, 8(7):e68796.

How to Cite
SHAHRIARI S, BAKHSHI M, SHAHVERDI AR, BERAHMEH A, SAFAVIFAR F, KHORRAMIZADEH MR. Targeted Intracellular Heat Transfer in Cancer Therapy: Assessment of Asparagine-laminated Gold Nanoparticles in Cell Model of T cell Leukemia. Iran J Public Health. 46(3):357-367.
Original Article(s)