Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells

Authors: Amaneh Javid, Shahin Ahmadian, Ali A. Saboury, Saeed Rezaei-Zarchi

Abstract:

This study determines the effect of naked and heparinbased super-paramagnetic iron oxide nanoparticles on the human cancer cell lines of A2780. Doxorubicin was used as the anticancer drug, entrapped in the SPIO-NPs. This study aimed to decorate nanoparticles with heparin, a molecular ligand for 'active' targeting of cancerous cells and the application of modified-nanoparticles in cancer treatment. The nanoparticles containing the anticancer drug DOX were prepared by a solvent evaporation and emulsification cross-linking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 110±15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of DOX from the SPIO-NPs was successful. Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell toxicity than the individual HP and confocal microscopy analysis confirmed excellent cellular uptake efficiency. These results indicate that HP based SPIO-NPs have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.

Keywords: Heparin, A2780 cells, ovarian cancer, nanoparticles, doxorubicin.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1328648

References:

[1] S. Nie, Y. Xing, G. J. Kim, and J. W. Simons, "Nanotechnology applications in cancer," Annu. Rev. Biomed. Eng. Vol. 9, pp. 257-288, 2007.
[2] C. C. M. You, O. R. Gider, B. Ghosh, S. P. Kim, I. Erdogan, B. Krovi, S. A. Bunz, U. H. F. Rotello, "Detection and identification of proteins using nanoparticle? Fluorescent polymer ÔÇÿchemical nose- sensors," Nature Nanotech. Vol. 2, pp. 318-323, 2007.
[3] M. Ferrari, "Cancer nanotechnology: opportunities and challenges," Nat Rev Cancer, vol. 5, pp. 161-71, 2005.
[4] S. Kommareddy, and M. Amiji, "Preparation and evaluation of thiolmodified gelatin nanoparticles for intracellular DNA delivery in response to glutathione," Bioconjug. Chem. vol. 16, 1423-1432, 2005.
[5] D. B. Pike, S. Cai, K. R. Pomraning, M. A. Firpo, R. J. Fisher, and X. Z. Shu, "Heparinregulated release of growth factors in vitro and angiogenic response in vivo to implanted hyaluronan hydrogels containing VEGF and bFGF," Biomaterials, vol. 27, pp. 5242-5251, 2006.
[6] R. J. Linhardt, "Heparin-induced cancer cell death," Chem. Biol. vol. 11, pp. 420-422, 2007.
[7] M. K. Yu, D. Y. Lee, Y. S. Kim, K. Park, S. A. Park, and D. H. Son, "Antiangiogenic and apoptotic properties of a novel amphiphilic folate- heparin-lithocholate derivative having cellular internality for cancer therapy," Pharm. Res. vol. 24, pp. 705-14, 2007.
[8] Q. L. Guo, Q. D. You, Z. Q. Wu, S. T. Yuan, and L. Zhao, "General gambogic acids inhibited growth of human hepatoma SMMC-7721 cells in vitro and in nude mice," Acta Pharmacol. Sin. vol. 25, pp. 769-774, 2004.
[9] Q. L. Guo, S. S. Lin, and Q. D. You, "Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells," Life Sci. vol. 78, pp. 1238-1245, 2006.
[10] Q. L. Guo, S. S. Lin, and Q. D. You, "Inhibition of human telomerase reverse transcriptase gene expression by gambogic acid in human hepatoma SMMC-7721 cells," Life Sci. vol. 78, pp. 1238-1245, 2006.
[11] T. T. Wang, J. Wei, X. P. Qian, Y. T. Ding, L. X. Yu, and B. R. Liu, "Gambogic acid, a potent inhibitor of survivin, reverses docetaxel resistance in gastric cancer cells," Cancer Lett. vol. 262, pp. 214-222, 2008.
[12] K. K. Gilles, and I. Joseph, "A nanoparticle-based immobilization assay for prion-kinetics study," J. Nanobiotechnol. Vol. 4, pp. 8-16, 2006.
[13] B. L. Lin, X. D. Shen, and S. Cui, "Application of nanosized Fe3O4 in anticancer drug carriers with target-orientation and sustained-release properties," Biomed. Mater. vol. 2, pp. 132-134, 2007.
[14] J. C. Reed, "Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance," Curr. Opin. Oncol. Vol. 7, pp. 541- 546, 1995.
[15] B. A. Chen, Q. Sun, and X. M. Wang, "Reveral in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/AO2 leukemic cells," Int. J. Nanomedicine, vol. 3, pp. 277-286, 2008.
[16] B. A. Chen, J. Cheng, and Y. N. Wu, "Reversal of multidrug resistance by magnetic Fe3O4 nanoparticle copolymerizating daunorubicin and 5- bromotetrandrine in xenograft nude-mice," Int. J. Nanomedicine, vol. 4, pp. 73-78, 2009.
[17] B. A. Chen, J. Cheng, and M. F. Shen, "Magnetic nanoparticle of Fe3O4 and 5-bromotetrandrin interact synergistically to induce apoptosis by daunorubicin in leukemia cells," Int. J. Nanomedicine, vol. 4, pp. 65-71, 2009.
[18] K. Yacobi, A. Wojtowicz, A. Tsafriri, and A. Gross, "Gonadotropins enhance caspase-3 and -7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture," Endocrinol. Vol. 145, pp. 1943-1951, 2004.
[19] N. Takai, T. Ueda, M. Nishida, K. Nasu, and K. Miyakawa, "The relationship between oncogene expression and clinical outcome in endometrial carcinoma," Curr. Cancer Drug Targets, vol. 4, pp. 511- 520, 2004.
[20] D. C. Altieri, "Survivin, versatile modulation of cell division and apoptosis in cancer," Oncogene. vol. 22, pp. 8581-8589, 2003.
[21] X. Ling, R. J. Bernacki, M. G. Brattain, and F. Z. Li, "Induction of survivin expression by taxol (paclitaxel) is an early event,which is independent of taxol mediated G2/M arrest," J. Biol. Chem. vol. 279, pp. 15196-15203, 2004.
[22] S. P. Tu, J. T. Cui, and P. Liston, "Gene therapy for colon cancer by adenoassociated viral vector-mediated transfer of survivin Cys84Ala mutant," Gastroenterol. vol. 128, pp. 361-375, 2005.
[23] D. C. Altieri, "Validating survivin as a cancer therapeutic target," Nat. Rev. Cancer, vol. 3, pp. 46-54, 2003.
[24] J. M. Adams, and S. Cory, "The Bcl-2 protein family: arbiters of cell survival," Science.vol. 281, pp. 1322-1326, 1998.
[25] H. J. M. M. Mertens, M. J. Heineman, and J. L. H. Evers, "The expression of apoptosis-related proteins bcl-2 and ki67 in endometrium of ovulatory men strual cycles," Gynecol. Obstet. Invest. vol. 53, pp. 224-230, 2002.
[26] C. M. J. L. Tilli, A. J. W. Stavast-Koey, F. C. S. Ramaekers, and H. A. M. Neumann, "Bax expression and growth behavior of basal cell carcinomas," J. Cutan. Pathol. vol. 29, pp. 79-87, 2002.
[27] F. Pettersson, A. G. Dalgleish, R. P. Bissonnette, and K. W. Colston, "Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-gamma and altered expression of Bcl-2/Bax," Br. J. Cancer. vol. 87, pp. 555-561, 2002.
[28] V. Kirkin, S. Joos, and M. Zornig, "The role of Bcl-2 family members in tumorigenesis," Biochim. Biophys. Acta. vol. 1644, pp. 229-249, 2004.
[29] A. Suzuki, T. Ito, and M. Hayashida, "Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death," Oncogene. vol. 19, pp. 1346-1353, 2000.