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Home > Journals > SCIREA Journal of Chemistry > Archive > Paper Information

Biomedical Applications of Zinc Oxide Nanomaterials in Cancer Treatment: A review

Volume 1, Issue 2, December 2016    |    PP. 67-89    |PDF (812 K)|    Pub. Date: December 23, 2016
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Satinder Pal Kaur Malhotra, Faculty of Science and Technology, ICFAI University, Rajawala Road, Selaqui Dehradun-248197, India
T. K. Mandal, Faculty of Science and Technology, ICFAI University, Rajawala Road, Selaqui Dehradun-248197, India

Zinc oxide (ZnO) is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. ZnO holds a unique optical, chemical sensing, semiconducting, electric conductivity and piezoelectric properties. One of the most important features of ZnO nanomaterials is low toxicity and biodegradability. ZnO nanoparticles (NPs) is a low-cost, low-toxic, and versatile material, have shown to have a promising future in biological applications. Specific properties and characteristics of ZnO NPs, such as their inherent toxicity against cancerous cells, at least for cells of lymphocytic origin, their ability to induce intracellular reactive oxygen species (ROS) generation leading to death via an apoptotic mechanism, and their physiochemical properties leading to cellular uptake and ease of functionalization make them an appealing candidate for biomedical applications. In this review, the current status of the use of ZnO nano-materials for biomedical applications, such as biomedical imaging, drug delivery, gene delivery and cancer therapy has been addressed.

Zinc oxide nanomaterial, cancer treatment, biomedical imaging, drug delivery, gene delivery, biomarker mapping

Cite this paper
Satinder Pal Kaur Malhotra, T. K. Mandal, Biomedical Applications of Zinc Oxide Nanomaterials in Cancer Treatment: A review, SCIREA Journal of Chemistry. Vol. 1 , No. 2 , 2016 , pp. 67 - 89 .


[ 1 ] Wang, Z.L. Splendid one-dimensional nanostructures of zinc oxide: a new nanomaterial family for nanotechnology. ACS Nano. 2008,2,1987.
[ 2 ] Yang,P.; Yan,R.; Fardy,M. Semiconductor nanowire: what's next? Nano Lett. 2010,10,1529.
[ 3 ] Huang ,M.H.; Wu,Y.; Feick, H. Catalytic Growth of Zinc Oxide Nanowires by Vapor Transport. Adv Mater. 2001,13,113.
[ 4 ] Fan, Z.; Lu, J.G. Zinc oxide nanostructures: synthesis and properties. J Nanosci Nanotechnol. 2005,5,1561.
[ 5 ] Wang, X.; Liu, J.; Song, J.; Wang, Z.L. Integrated nanogenerators in biofluid. Nano Lett. 2007,7,2475.
[ 6 ] Lao, C.S.; Park, M.C.; Kuang, Q. Giant enhancement in UV response of ZnO nanobelts by polymer surface-functionalization. J Am Chem Soc. 2007,129,12096.
[ 7 ] Yakimova, R.; Selegard, L.; Khranovskyy, V. ZnO materials and surface tailoring for biosensing. Front Biosci (Elite Ed) 2012,4,254.
[ 8 ] Yang,Y.; Guo, W. Y. Piezotronic effect on the output voltage of P3HT/ZnO micro/nanowire heterojunction solar cells. Nano Lett. 2011,11,4812.
[ 9 ] Ozgur, U.;Alivov, Y.I.; Liu,C. A comprehensive review of ZnO materials and devices. J Appl Phys. 2005,98,041301.
[ 10 ] Nohynek,G.J.; Dufour, E.K.; Roberts, M.S. Nanotechnology, cosmetics and the skin: is there a health risk? Skin Pharmacol Physiol. 2008,6,49.
[ 11 ] Nohynek, G.J.; Lademann ,J; Ribaud C.; Roberts, M.S. Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety. Crit Rev Toxicol. 2007,37,251.
[ 12 ] Liu, D.; Wu, W.; Qiu, Y. Surface functionalization of ZnO nanotetrapods with photoactive and electroactive organic monolayers. Langmuir. 2008,24,5052.
[ 13 ] Taratula, O.; Galoppin, E.; Wang, D. Binding studies of molecular linkers to ZnO and MgZnO nanotip films. J Phys Chem B. 2006,110,6506.
[ 14 ] Zhou, J.; Xu N.S.; Wang Z.L. Dissolving Behavior and Stability of ZnO Wires in Biofluids: A Study on Biodegradability and Biocompatibility of ZnO Nanostructures. Adv Mater. 2006,18,2432.
[ 15 ] Zhou, J; Xu, N.S.; Wang, Z.L. Dissolving behavior and stability of ZnO wires in biofluids: a study on biodegradability and biocompatibility of ZnO nanostructures. Adv Mater. 2006,18,2432.
[ 16 ] Huang, K.; Ma, H.;Liu J.; Huo, S.; Kumar, A.; Wei, T. Size-dependent localization and penetration of ultrasmall gold nanoparticles in cancer cells, multicellular spheroids, and tumors in vivo. ACSNano.2012,6,4483.
[ 17 ] Hanley, C.; Layne, J.; Punnoose, A. Preferential killing of cancer cells and activated human T cells using zinc oxide nanoparticles. Nanotech. 2008,19,295103.
[ 18 ] Wang,H.; Wingett, D.; Engelhard, M.H. Fluorescent dye encapsulated ZnO particles with cell-specific toxicity for potential use in biomedical applications. J Mater Sci Mater Med. 2009,20,11.
[ 19 ] Abercrombie, M.; Ambrose, E.J. The surface properties of cancer cells: a review. Cancer Res. 1962,22,525.
[ 20 ] Bockris, J.O.M.; Habib, M.A. Are there electrochemical aspects of cancer? J Biol Physics. 1982,10,227.
[ 21 ] Papo, N.; Shahar, M.; Eisenbach, L.; Shai ,Y. A novel lytic peptide composed of DL-amino acids selectively kills cancer cells in culture and in mice. J Biol Chem. 2003,278,21018.
[ 22 ] Shrode, L.D.;Tapper, H.; Grinstein, S. Role of intracellular pH in proliferation, transformation, and apoptosis. J Bioenerg Biomembr. 1997,29,393.
[ 23 ] Rich, I.N.; Worthington-White, D.; Garden, O.A.;Musk P. Apoptosis of leukemic cells accompanies reduction in intracellular pH after targeted inhibition of the Na(+)/H(+) exchanger. Blood. 2000,95,1427.
[ 24 ] Guo, D.; Wu, C; Jiang,H. Synergistic cytotoxic effect of different sized ZnO nanoparticles and daunorubicin against leukemia cancer cells under UV irradiation. J Photochem Photobiol B. 2008,93,119.
[ 25 ] Nair, S.; Sasidharan, A.; Divya Rani, V. Role of size scale of ZnO nanoparticles and microparticles on toxicity toward bacteria and osteoblast cancer cells. J Mater Sci Mater Med. 2009,20,235.
[ 26 ] Hanley, C., Thurber, A., Hanna, C. The influences of cell type and ZnO nanoparticle size and immune cell cytotoxicity and cytokine induction. Nanoscale Res Lett. 2009,4,1409.
[ 27 ] Brannon-Peppas, L.; Blanchette, J.O. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev. 2004,56,1649.
[ 28 ] Zhou, J.; Xu N.;Wang, Z.L. Dissolving behavior and stability of ZnO wires in biofluids: A study on biodegradability and biocompatibility. Adv Mater. 2006,18,2432.
[ 29 ] Wang, R.M.; Xing, Y.J.; Yu, D.P. Fabrication and microstructure analysis on zinc oxide nanotubes. New J Physics. 2003,5,115.
[ 30 ] Wu, H.Q.; Wei, X.W.; Shao, M.W.; Gu, J.S. Synthesis of zinc oxide nanorods using carbon nanotubes as templates. J Crystal Growth. 2004,265,184.
[ 31 ] Mortimer, M.; Kasemets, K.; Kahru, A. Toxicity of ZnO and CuO nanoparticles to ciliated protozoa Tetrahymena thermophila. Toxicol. 2010,269,182.
[ 32 ] Franklin, N.M.; Rogers, N.J.; Apte S.C. Comparative toxicity of nanoparticulate ZnO, bulk ZnO, and ZnCl2 to a freshwater microalga (Pseudokirchneriella subcapitata): the importance of particle solubility. Environ Sci Technol. 2007,41,8484.
[ 33 ] Kasemets, K.; Ivask,A.; Dubourguier, H.C.;Kahru, A. Toxicity of nanoparticles of ZnO, CuO and TiO2 to yeast Saccharomyces cerevisiae. Toxicol In Vitro. 2009,23,1116.
[ 34 ] Zhu, X.; Zhu, L.; Duan, Z.Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2008,43,278.
[ 35 ] Nel, A.; Xia T.; Madler, L.; Li, N. Toxic potential of materials at the nanolevel. Sci. 2006,311,622.
[ 36 ] Deng ,X.; Luan, Q.; Chen, W. Nanosized zinc oxide particles induce neural stem cell apoptosis. Nanotech. 2009,20,115101.
[ 37 ] Brunner, T.J.; Wick, P.; Manser, P. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol. 2006,40,4374.
[ 38 ] Shankar, A.H.; Prasad, A.S. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998,68,447S.
[ 39 ] Lim, N.C.; Freake, H.C.;.Bruckner,C. Illuminating zinc in biological systems. Chem. 2004,11,38.
[ 40 ] Choi, D.W.; Koh, J.Y. Zinc and brain injury. Annu Rev Neurosci. 1998,21,347.
[ 41 ] Sayes, C.M.; Reed, K.L.; Warheit, D.B. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci. 2007,97,163.
[ 42 ] Shen, C.; James, S.A.;de Jonge, M.D.;Turney, T.W.; Wright, P.F.; Feltis, B.N. Relating cytotoxicity, zinc ions, and reactive oxygen in ZnO nanoparticle-exposed human immune cells. Toxicol Sci. 2013,136,120.
[ 43 ] Rasmussen, J.W.; Martinez, E.; Louka, P.; Wingett, D.G. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert Opin Drug Deliv. 2010;7,1063.
[ 44 ] Moghimi, S. M.; Rajabi-Siahboomi, A. R. Adv. Drug Deliver. Rev. 2000, 41, 129.
[ 45 ] Jaracz, S.; Chen, J.; Kuznetsova, L. V.; Ojima, I. Bioorg. Med. Chem. 2005, 13, 5043.
[ 46 ] Antony, A. C. Folate receptors. Annu. Rev. Nutr. 1996, 16, 501
[ 47 ] Lu, Y.; Low, P. S. Adv. Drug Deliver. Rev. 2002, 54, 675.
[ 48 ] Maziarz, K. M.; Monaco, H. L.; Shen, F.; Ratnam, M. J. Biol. Chem. 1999, 274, 11086.
[ 49 ] Weitman, S. D.; Lark, R. H.; Coney, L. R.; Fort, D. W.; Frasca, V.; Zurawski, V. R. Jr.; Kamen, B. A. Cancer Res. 1992, 52, 3396.
[ 50 ] Ke, C.J.; Su, T.Y.; Chen, H.L.; Liu, H.L.; Chiang, W.L.; Chu, P.C.; Xia, Y.N.; Sung, H.W. Smart multifunctional hollow microspheres for the quick release of drugs in intracellular lysosomal compartments. Angew. Chem. Int. Ed. 2011, 50, 8086.
[ 51 ] Jin, E.; Zhang, B.; Sun, X.R.; Zhou, Z.X.; Ma, X.P.; Sun, Q.H.; Tang, J.B.; Shen, Y.Q.; Van Kirk, E.; Murdoch, W.J.; Radosz, M. Acid-active cell-penetrating peptides for in vivo tumor-targeted drug delivery. J. Am. Chem. Soc. 2013, 135, 933.
[ 52 ] Pearce,T.R.; Shroff, K.; Kokkoli, E. Peptide targeted lipid nanoparticles for anticancer drug delivery. Adv. Mater. 2012, 24, 3803.
[ 53 ] Wang, Y.H.; Song, S.Y.; Liu, J.H.; Liu, D.P.; Zhang, H.J. ZnO-functionalized upconverting nanotheranostic agent: Multi-modality imaging-guided chemotherapy with on-demand drug release triggered by pH. Angew. Chem. Int. Ed. 2015, 54, 536.
[ 54 ] Lin, Y.S.; Hurley, K.R.; Haynes, C.L. Critical considerations in the biomedical use of mesoporous silica nanoparticles. J. Phys. Chem. Lett. 2012, 3, 364.
[ 55 ] Zhu, J.; Liao, L.; Bian, X.J.; Kong, J.L.; Yang, P.Y.; Liu, B.H. pH-Controlled delivery of doxorubicin to cancer cells, based on small mesoporous carbon nanospheres. Small, 2012, 8, 2715.
[ 56 ] Zhang, Z.Y.; Xu, Y.D.; Ma, Y.Y.; Qiu, L.L.; Wang, Y.; Kong, J.L.; Xiong, H.M. Biodegradable ZnO@polymer core–shell nanocarriers: pH-triggered release of doxorubicin in vitro. Angew. Chem. Int. Ed. 2013, 52, 4127.
[ 57 ] Rasmussen, J.W.; Martinez, E.; Louka, P.; Wingett, D.G. Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert Opin. Drug Deliv. 2010, 7, 1063.
[ 58 ] Yuan, Q.; Hein, S.; Misra, R. D. K. Acta Biomater. 2010, 6, 2732.
[ 59 ] Yuan, Q.; Venkatasubramanian, R.; Hein, S.; Misra, R. D. K. Acta Biomater. 2008, 4, 1024.
[ 60 ] Zhang, J.; Misra, R. D. K. Acta Biomater. 2007, 3, 838.
[ 61 ] Muhammad, F.; Guo, M.; Guo, Y.; Qi, W.; Qu, F.; Sun, F.; Zhao, H.; Zhu, G. J. Mater. Chem. 2011, 21, 13406.
[ 62 ] Weng, K. C.; Noble, C. O.; Papahadjopoulos-Sternberg, B.; Chen, F. F.; Drummond, D. C.; Kirpotin, D. B.; Wang, D.; Hom, Y. K.; Hann, B.; Park, J. W. Nano Lett. 2008, 8, 2851.
[ 63 ] Lauffer, R. B. Chem. Rev. 1987, 87, 901.
[ 64 ] Mulder, W. J. M.; Strijkers, G. J.; van Tilborg, G. A. F.; Griffioen, A. W.; Nicolay, K. NMR Biomed. 2006, 19, 142.
[ 65 ] Bridot, J. L.; Faure, A. C.; Laurent, S.; Rivière, C.; Billotey, C.; Hiba, B.; Janier, M.; Josserand, V.; Coll, J. L.; Elst, L. V.; Muller, R.; Roux, S.; Perriat, P.; Tillement, O. J. Am. Chem. Soc. 2007, 129, 5076.
[ 66 ] Tsai, C. P.; Hung, Y.; Chou, Y. H.; Huang, D. M.; Hsiao, J. K.; Chang, C.; Chen, Y. C.; Mou, C. Y. Small. 2008, 4, 186.
[ 67 ] Lewin, M.; Carlesso, N.; Tung, C. H.; Tang, X. W.; Cory, D.; Scadden, D. T.; Weissleder, R. Nat. Biotechnol. 2000, 18, 410.
[ 68 ] Li, I. F.; Yeh, C. S. J. Mater. Chem. 2010, 20, 2079.
[ 69 ] Santra, S.; Yang, H.; Holloway, P. H.; Stanley, J. T.; Mericle, R. A. J. Am. Chem. Soc. 2005, 127, 1656.
[ 70 ] Wang, S.; Jarrett, B. R.; Kauzlarich, S. M.; Louie, A. Y. J. Am. Chem. Soc. 2007, 129, 3848.
[ 71 ] Ai, K.; Zhang, B.; Lu, L. Angew. Chem. Int. Ed. 2009, 48, 304.
[ 72 ] Drummond, D. C.; Meyer, O.; Hong, K.; Kirpotin, D. B.; Papahadjopoulos, D. Pharmacol. Rev. 1999, 51, 691.
[ 73 ] Medintz, I. L.; Uyeda, H. T.; Goldman, E. R.; Mattoussi, H. Nat. Mater. 2005, 4, 435.
[ 74 ] Liu, Y.; Ai, K.; Yuan, Q.; Lu, L. Biomater. 2011, 32, 1185.
[ 75 ] Norris, D. J.; Efros, A. L.; Erwin, S. C. Science. 2008, 319, 1776.
[ 76 ] Figdor, C.G.; de Vries, I.J.; Lesterhuis, W.J.; Melief C.J. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004,10,475.
[ 77 ] Cho, N.H.; Cheong, T.C.; Min, J.H. A multifunctional core-shell nanoparticle for dendritic cell-based cancer immunotherapy. Nat Nanotechnol. 2011,6,675.
[ 78 ] Hong, H.; Shi, J.; Yang, Y. Cancer-targeted optical imaging with fluorescent zinc oxide nanowires. Nano Lett. 2011,11,3744.
[ 79 ] Shi, J.; Hong, H.; Ding, Y. Evolution of Zinc Oxide Nanostructures through Kinetics Control. J Mater Chem. 2011,21,9000.
[ 80 ] Cai, W.; Chen, X. Anti-angiogenic cancer therapy based on integrin avb3 antagonism. Anti-Cancer Agents Med Chem. 2006,6,407.
[ 81 ] Cai, W.; Niu, G.; Chen X. Imaging of integrins as biomarkers for tumor angiogenesis. Curr Pharm Des. 2008,14,2943.
[ 82 ] Hong, H.; Shi, J.; Yang, Y. Cancer-targeted optical imaging with fluorescent zinc oxide nanowires. Nano Lett. 2011,11,3744.
[ 83 ] Roberts, M.S.; Roberts, M.J.; Robertson, T.A.; Sanchez, W.; Thörling, C.; Zou, Y.H.; Zhao, X.; Becker, W.; Zvyagin, A.V. In vitro and in vivo imaging of xenobiotic transport in human skin and in the rat liver. J. Biophoton. 2008, 1, 478.
[ 84 ] Zhang, W.Q.; Lu,Y.; Zhang,T.K. Controlled Synthesis and Biocompatibility of Water-Soluble ZnO Nanorods/Au Nanocomposites with Tunable UV and Visible Emission Intensity. J Phys Chem C. 2008,112,19872.
[ 85 ] Brown, S.B.; Brown, E.A.; Walker, I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004,5,497. 86. Wilson, B.C.; Patterson, M.S. The physics, biophysics and technology of photodynamic therapy. Phys Med Biol. 2008, 53,R61.
[ 86 ] Zhang, H.; Chen, B.; Jiang, H. A strategy for ZnO nanorod mediated multi-mode cancer treatment. Biomaterials. 2011,32,1906.
[ 87 ] Hu, Z.; Li, J.; Li, C.; Zhao, S.; Li, N.; Wang, Y.; Wei, F.; Chen, L.; Huang Y.Folic acid-conjugated graphene–ZnO nanohybrid for targeting photodynamic therapy under visible light irradiation J. Mater chem., B.2013,1,5003.
[ 88 ] Zhang, Z.Y.; Xu, Y.D.; Ma, Y.Y.; Qui, L.L.; Wang, Y.; Kong, J.L. Biodegradable ZnO@polymer Core–Shell Nanocarriers: pH-Triggered Release of Doxorubicin In Vitro.  Angewandte Chemie Inter.Edition 2013, 52, 4127.
[ 89 ] Zeng,K.; Li,J.; Zhang, Z.; Yan, M.; Liao,Y.; Zhang X,; Zhao, C. Lipid-coated ZnO nanoparticles as lymphatic-targeted drug carriers: study on cell-specific toxicity in vitro and ymphatic targeting in vivo J. Mater. Chem. B, 2015, 3, 5249.
[ 90 ] Geho, D.H.; Lahar, N.; Ferrari, M.; Petricoin, E.F.; Liotta L.A. Opportunities for nanotechnology-based innovation in tissue proteomics. Biomed. Microdevices. 2004, 6, 231.
[ 91 ] Wang,D.; Li, Y.; Lin, Z.; Qiu, B.; Guo, L. Surface-enhanced electrochemiluminescence of Ru@SiO2 for ultrasensitive detection of carcinoembryonic antigen. Anal. Chem. 2015, 87, 5966.
[ 92 ] Wang, Y.; Jug, L. Ultrasensitive rapid detection of human serum antibody biomarkers by biomarker-capturing viral nanofibers. ACS Nano .2015, 9, 4475.
[ 93 ] Shen, W.; Xiong, H.; Xu, Y. ZnO-poly(methyl methacrylate) nanobeads for enriching and desalting low-abundant proteins followed by directly MALDI-TOF MS analysis. Anal Chem. 2008, 80,6758.
[ 94 ] Dorfman, A.; Parajuli, O.; Kumar, N.; Hahm, J.I. Novel telomeric repeat elongation assay performed on zinc oxide nanorod array supports. J Nanosci Nanotechnol. 2008, 8, 410.
[ 95 ] McCormick, F. Cancer gene therapy: fringe or cutting edge? Nat Rev Cancer. 2001, 1, 130.
[ 96 ] Nie, L.; Gao, L.; Feng, P. Three-dimensional functionalized tetrapod-like ZnO nanostructures for plasmid DNA delivery. Small. 2006, 2, 621.
[ 97 ] Nie, L.; Gao, L.; Yan, X.; Wang, T. Functionalized tetrapod-like ZnO nanostructures for plas mid DNA purification, polymerase chain reaction and delivery. Nanotech. 2007,18,015101.
[ 98 ] Zhang, P.; Liu, W. ZnO QD@PMAA-co-PDMAEMA nonviral vector for plasmid DNA delivery and bioimaging. Biomater. 2010,31,3087.

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