In vitro and in vivo Anticancer Activity of Nanosize Zinc Oxide Composites of Doxorubicin
The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.
[1] J. K. Vasir, and V. Labhasetwar, "Targeted drug delivery in cancer therapy,” Technol. Cancer Res. Treat., vol. 4, pp. 363-374, Aug. 2005.
[2] K. Deepak, J. Deepti, S. Vivek, K. Rajendra, and A. T. Patil, "Cancer therapeutics - opportunities, challenges and advances in drug delivery,” JAPS, vol. 01 (09), pp. 1-10, 2011.
[3] D. R. Paul, and L. M. Robeson, "Polymer nanotechnology: Nanocomposites,” Polymer, vol. 49, pp. 3187–3204, 2008.
[4] V. K. Varadan, A. S. Pillai, D. Mukherji, M. Dwivedi, and L. Chen, "Nanoscience and nanotechnology in engineering,” in Nanoscale Fabrication and Characterization, Singapore: World Scientific, 2010, pp-71-105.
[5] G. Pasut, M. Sergi, F. M. Veronese, "Anti-cancer PEG-enzymes: 30 years, old, but still a current approach,” Adv. Drug Deliv. Rev., vol. 60(1), pp. 69–78, 2008.
[6] K. Greish, "Enhanced permeability and retention of macromolecular drugs in solid tumors: a royal gate for targeted anticancer nanomedicines.” J. Drug Target. vol. 15(7–8), pp. 457–464, 2007
[7] M. J. Santander-Ortega, T. Staunerc, B. Loretzb, J. L. Ortega-Vinuesaa, D. Bastos-González, G. Wenzc, U. F. Schaefer, and C. M. Lehr, "Nanoparticles made from novel starch derivatives for transdermal drug delivery,” J. Control Release, vol. 141, pp. 85–92, 2010.
[8] R. Gref, J. Rodrigues, and P. Couvreur, "Polysaccharides grafted with polyesters: novel amphiphilic copolymers for biomedical applications,” Macromolecules, vol. 35 (27), pp. 9861–9867, 2002.
[9] J. J. Listinsky, G. P. Siegal, and C. M. Listinsky, "Alpha-L-fucose - a potentially critical molecule in pathologic processes including neoplasia,” Am. J. Clin. Pathol., vol. 110 (4), pp. 425–440, 1998.
[10] E. Osterberg, K. Bergstrom, K. Holmberg, T. P. Schuman, J. A. Riggs, N. L. Burns, J. M. Vanalstine, and J. M. Harris, "Protein-rejecting ability of surface-bound dextran in endon and side-on configurations - comparison to Peg,” J. Biomed. Mater. Res., vol. 29 (6), pp. 741–747, 1995.
[11] S. Jevsevar, M. Kunstelj, and V.G. Porekar, "PEGylation of therapeutic proteins,” Biotechnol. J. vol. 5 (1), pp. 113–128, 2010.
[12] A. P. Marques, R. L. Reis, and J. A. Hunt, "The biocompatibility of novel starch-based polymers and composites: in vitro studies,” Biomaterials, vol. 23 (6), pp. 1471–1478, 2002.
[13] M. A. Araujo, A. M. Cunha, and M. Mota, "Enzymatic degradation of starch-based thermoplastic compounds used in protheses: identification of the degradation products in solution,” Biomaterials, vol. 25 (13), pp. 2687–2693, 2004.
[14] N. G. Portney, M. Ozkan. Nano-oncology: drug delivery, imaging, and sensing. Anal Bioanal Chem 384: pp.620–630, 2006.
[15] M. Rawat, D. Singh, S. Saraf, S.Saraf. Nanocarriers: promising vehicle for bioactive drugs. Biol Pharm Bull 29:pp.1790–1798, 2006.
[16] J.L. Fraikin, T. M. Teesalu, C.M. McKenney, E. Ruoslahti & N Andrew, Cleland (). A high-throughputlabel-free nanoparticle analyser. Nature Nanotechnology 6: pp.308-313, 2011.
[17] S. Ostrovsky, G. Kazimirsky, A. Gedanken, and C. Brodie, "Selective cytotoxic effect of ZnO nanoparticles on glioma cells,” Nano Res., vol. 2 (11), pp. 882- 890, Nov. 2009.
[18] E. Arakelova, A. Khachatryan, K. Avjyan, Z. Farmazyan, A. Mirzoyan, L. Savchenko, S. Ghazaryan, and F. Arsenyan, "Zinc oxide nanocomposites with antitumor activity,” Natural Science, vol. 2 (12), pp. 1341-1348, 2010.
[19] E. Arakelova, A. Khachatryan, K. Avdjyan, Z. Farmazyan, L. Savshenko, A. Mirzoyan, S. Ghazaryan, and F. Arsenyan, "Method of obtaining anticancer composite films and coatings,” Patent application of Republic of Armenia, № 2010-0053 from 07.05.10.
[20] A. A. van de Loosdrecht, R. H. J. Beelen, G. J. Ossenkoppele, M. G. Broekhoven, and M. M. A. C. Langenhuijsen, "A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia,” J. Immunol. Methods, vol. 174 (1-2), pp. 311-320, Sept. 1994.
[21] W. Strober, "Trypan blue exclusion test of cell viability," Curr. Protoc. Immunol., Appendix 3: Appendix 3B, May 2001.
[22] R. B. Badisa, S. F. Darling-Reed, P. Joseph, J. S. Cooperwood, L. M. Latinwo, and C. B. Goodman, "Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells,” Anticancer Res., vol. 29, pp. 2993-2996, 2009.
[23] P. Pozarowski, and Z. Darzynkiewicz, "Analysis of cell cycle by flow cytometry," Methods Mol. Biol., vol. 281, pp. 301-311, 2004.
[24] Y. Deshan, Z. Y. Choe, Y. H. Zhao, Q. H. Ming-Ching, and P. Ping, "Cellular penetration and localization of polyethylene glycol,” Proc. Amer. Assoc. Cancer Res., vol. 45, p. 149-a, 2004.
[25] F. M. Veronese, O. Schiavon, G. Pasut, R. Mendichi, L. Andersson, A.Tsirk, J.Ford, G. Wu, S. Kneller, J. Davies, and R. Duncan, "Peg – doxorubicin conjugates: influence of polymer structure on drug release in in vitro cytotoxicity, biodistribution, and antitumor activity,” Bioconjugate Chem., vol. 16 (4), pp. 775–784, 2005.
[26] A. Schimmer, and I. Tannock, "Discovery and evaluation of anticancer drugs,” in Basic Science of Oncology, 5th ed., I. Tannock and R. Hill, Eds, New York: McGraw-Hill, 2013, pp. 393-419.
[27] E. J. Park, H. K. Kwon, Y. M. Choi, H. J. Shin, and S. Choi, "Doxorubicin induces cytotoxicity through upregulation of perk–dependent ATF3,” PLoS ONE, vol. 7(9), e44990, doi:10.1371/journal.pone.0044990, 2012.
[28] I. M. Ghobrial, T. E. Witzig, and A. A. Adjei, "Targeting apoptosis pathways in cancer therapy,” CA Cancer J Clin, vol. 55 (3), pp. 139–198, Feb. 2009.
[29] B. Barlogie, B. Drewinko, D.A. Johnston, and E.J. Freireich, "The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line,” Cancer Res., vol. 36, pp. 1975-1979, Jun 1976.
[30] C. O'Loughlin, M. Heenan, S. Coyle, and M. Clynes, "Altered cell cycle response of drug-resistant lung carcinoma cells to doxorubicin,” Eur. J. Cancer, vol. 36, pp. 1149-1160, 2000.
[31] J. Emami, "In vitro - in vivo correlation: from theory to applications,” J. Pharm. Pharmaceut. Sci., vol. 9(2), pp. 169-189, 2006.
[32] S. Arora, J. M. Rajwade, and K. M. Paknikar, "Nanotoxicology and in vitro studies: The need of the hour,” Toxicol. Appl. Pharmacol., vol. 258, pp. 151–165, 2012.
[33] X. Han, N. Corson, P. Wade-Mercer, R. Gelein, J. Jiang, M. Sahu, P. Biswas, J. N. Finkelstein, A. Elder, and G. Oberdörster, "Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data,” Toxicology, vol. 16;297(1-3), pp. 1–9, July 2012.
[34] C.M. Sayes, K.L. Reed, D.B. Warheit, "Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles,” Toxicol. Sci., vol. 97, pp. 163–180, Apr. 2012.
[35] N. Desai, "Challenges in Development of Nanoparticle-Based Therapeutics,” AAPS J., vol. 14(2), pp. 282–295, 2012.
[1] J. K. Vasir, and V. Labhasetwar, "Targeted drug delivery in cancer therapy,” Technol. Cancer Res. Treat., vol. 4, pp. 363-374, Aug. 2005.
[2] K. Deepak, J. Deepti, S. Vivek, K. Rajendra, and A. T. Patil, "Cancer therapeutics - opportunities, challenges and advances in drug delivery,” JAPS, vol. 01 (09), pp. 1-10, 2011.
[3] D. R. Paul, and L. M. Robeson, "Polymer nanotechnology: Nanocomposites,” Polymer, vol. 49, pp. 3187–3204, 2008.
[4] V. K. Varadan, A. S. Pillai, D. Mukherji, M. Dwivedi, and L. Chen, "Nanoscience and nanotechnology in engineering,” in Nanoscale Fabrication and Characterization, Singapore: World Scientific, 2010, pp-71-105.
[5] G. Pasut, M. Sergi, F. M. Veronese, "Anti-cancer PEG-enzymes: 30 years, old, but still a current approach,” Adv. Drug Deliv. Rev., vol. 60(1), pp. 69–78, 2008.
[6] K. Greish, "Enhanced permeability and retention of macromolecular drugs in solid tumors: a royal gate for targeted anticancer nanomedicines.” J. Drug Target. vol. 15(7–8), pp. 457–464, 2007
[7] M. J. Santander-Ortega, T. Staunerc, B. Loretzb, J. L. Ortega-Vinuesaa, D. Bastos-González, G. Wenzc, U. F. Schaefer, and C. M. Lehr, "Nanoparticles made from novel starch derivatives for transdermal drug delivery,” J. Control Release, vol. 141, pp. 85–92, 2010.
[8] R. Gref, J. Rodrigues, and P. Couvreur, "Polysaccharides grafted with polyesters: novel amphiphilic copolymers for biomedical applications,” Macromolecules, vol. 35 (27), pp. 9861–9867, 2002.
[9] J. J. Listinsky, G. P. Siegal, and C. M. Listinsky, "Alpha-L-fucose - a potentially critical molecule in pathologic processes including neoplasia,” Am. J. Clin. Pathol., vol. 110 (4), pp. 425–440, 1998.
[10] E. Osterberg, K. Bergstrom, K. Holmberg, T. P. Schuman, J. A. Riggs, N. L. Burns, J. M. Vanalstine, and J. M. Harris, "Protein-rejecting ability of surface-bound dextran in endon and side-on configurations - comparison to Peg,” J. Biomed. Mater. Res., vol. 29 (6), pp. 741–747, 1995.
[11] S. Jevsevar, M. Kunstelj, and V.G. Porekar, "PEGylation of therapeutic proteins,” Biotechnol. J. vol. 5 (1), pp. 113–128, 2010.
[12] A. P. Marques, R. L. Reis, and J. A. Hunt, "The biocompatibility of novel starch-based polymers and composites: in vitro studies,” Biomaterials, vol. 23 (6), pp. 1471–1478, 2002.
[13] M. A. Araujo, A. M. Cunha, and M. Mota, "Enzymatic degradation of starch-based thermoplastic compounds used in protheses: identification of the degradation products in solution,” Biomaterials, vol. 25 (13), pp. 2687–2693, 2004.
[14] N. G. Portney, M. Ozkan. Nano-oncology: drug delivery, imaging, and sensing. Anal Bioanal Chem 384: pp.620–630, 2006.
[15] M. Rawat, D. Singh, S. Saraf, S.Saraf. Nanocarriers: promising vehicle for bioactive drugs. Biol Pharm Bull 29:pp.1790–1798, 2006.
[16] J.L. Fraikin, T. M. Teesalu, C.M. McKenney, E. Ruoslahti & N Andrew, Cleland (). A high-throughputlabel-free nanoparticle analyser. Nature Nanotechnology 6: pp.308-313, 2011.
[17] S. Ostrovsky, G. Kazimirsky, A. Gedanken, and C. Brodie, "Selective cytotoxic effect of ZnO nanoparticles on glioma cells,” Nano Res., vol. 2 (11), pp. 882- 890, Nov. 2009.
[18] E. Arakelova, A. Khachatryan, K. Avjyan, Z. Farmazyan, A. Mirzoyan, L. Savchenko, S. Ghazaryan, and F. Arsenyan, "Zinc oxide nanocomposites with antitumor activity,” Natural Science, vol. 2 (12), pp. 1341-1348, 2010.
[19] E. Arakelova, A. Khachatryan, K. Avdjyan, Z. Farmazyan, L. Savshenko, A. Mirzoyan, S. Ghazaryan, and F. Arsenyan, "Method of obtaining anticancer composite films and coatings,” Patent application of Republic of Armenia, № 2010-0053 from 07.05.10.
[20] A. A. van de Loosdrecht, R. H. J. Beelen, G. J. Ossenkoppele, M. G. Broekhoven, and M. M. A. C. Langenhuijsen, "A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia,” J. Immunol. Methods, vol. 174 (1-2), pp. 311-320, Sept. 1994.
[21] W. Strober, "Trypan blue exclusion test of cell viability," Curr. Protoc. Immunol., Appendix 3: Appendix 3B, May 2001.
[22] R. B. Badisa, S. F. Darling-Reed, P. Joseph, J. S. Cooperwood, L. M. Latinwo, and C. B. Goodman, "Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells,” Anticancer Res., vol. 29, pp. 2993-2996, 2009.
[23] P. Pozarowski, and Z. Darzynkiewicz, "Analysis of cell cycle by flow cytometry," Methods Mol. Biol., vol. 281, pp. 301-311, 2004.
[24] Y. Deshan, Z. Y. Choe, Y. H. Zhao, Q. H. Ming-Ching, and P. Ping, "Cellular penetration and localization of polyethylene glycol,” Proc. Amer. Assoc. Cancer Res., vol. 45, p. 149-a, 2004.
[25] F. M. Veronese, O. Schiavon, G. Pasut, R. Mendichi, L. Andersson, A.Tsirk, J.Ford, G. Wu, S. Kneller, J. Davies, and R. Duncan, "Peg – doxorubicin conjugates: influence of polymer structure on drug release in in vitro cytotoxicity, biodistribution, and antitumor activity,” Bioconjugate Chem., vol. 16 (4), pp. 775–784, 2005.
[26] A. Schimmer, and I. Tannock, "Discovery and evaluation of anticancer drugs,” in Basic Science of Oncology, 5th ed., I. Tannock and R. Hill, Eds, New York: McGraw-Hill, 2013, pp. 393-419.
[27] E. J. Park, H. K. Kwon, Y. M. Choi, H. J. Shin, and S. Choi, "Doxorubicin induces cytotoxicity through upregulation of perk–dependent ATF3,” PLoS ONE, vol. 7(9), e44990, doi:10.1371/journal.pone.0044990, 2012.
[28] I. M. Ghobrial, T. E. Witzig, and A. A. Adjei, "Targeting apoptosis pathways in cancer therapy,” CA Cancer J Clin, vol. 55 (3), pp. 139–198, Feb. 2009.
[29] B. Barlogie, B. Drewinko, D.A. Johnston, and E.J. Freireich, "The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line,” Cancer Res., vol. 36, pp. 1975-1979, Jun 1976.
[30] C. O'Loughlin, M. Heenan, S. Coyle, and M. Clynes, "Altered cell cycle response of drug-resistant lung carcinoma cells to doxorubicin,” Eur. J. Cancer, vol. 36, pp. 1149-1160, 2000.
[31] J. Emami, "In vitro - in vivo correlation: from theory to applications,” J. Pharm. Pharmaceut. Sci., vol. 9(2), pp. 169-189, 2006.
[32] S. Arora, J. M. Rajwade, and K. M. Paknikar, "Nanotoxicology and in vitro studies: The need of the hour,” Toxicol. Appl. Pharmacol., vol. 258, pp. 151–165, 2012.
[33] X. Han, N. Corson, P. Wade-Mercer, R. Gelein, J. Jiang, M. Sahu, P. Biswas, J. N. Finkelstein, A. Elder, and G. Oberdörster, "Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data,” Toxicology, vol. 16;297(1-3), pp. 1–9, July 2012.
[34] C.M. Sayes, K.L. Reed, D.B. Warheit, "Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles,” Toxicol. Sci., vol. 97, pp. 163–180, Apr. 2012.
[35] N. Desai, "Challenges in Development of Nanoparticle-Based Therapeutics,” AAPS J., vol. 14(2), pp. 282–295, 2012.
@article{"International Journal of Medical, Medicine and Health Sciences:66277", author = "E. R. Arakelova and S. G. Grigoryan and F. G. Arsenyan and N. S. Babayan and R. M. Grigoryan and N. K. Sarkisyan", title = "In vitro and in vivo Anticancer Activity of Nanosize Zinc Oxide Composites of Doxorubicin ", abstract = "The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.
", keywords = "Anticancer activity, cancer specificity, doxorubicin, zinc oxide.", volume = "8", number = "1", pages = "33-6", }
