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Nanooncology pp 341–364Cite as

Metal/Metal Oxide Nanoparticles for Cancer Therapy

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Part of the book series: Nanomedicine and Nanotoxicology ((NANOMED))

Abstract

Cancer includes a large group of affections that are characterized by an uncontrolled cellular growth and the ability of these cells to spread to distant sites. The uncontrolled cellular growth in cancer cells is attributed to a failure in programmed cell death or apoptosis in which a possible role of oxidative stress has been described. Moreover, oxidative stress is involved in carcinogenesis by influencing intracellular signal transduction and transcription factors directly or indirectly via antioxidants. Metal and metal oxide nanoparticles (NPs) have emerged as innovative tools to address the development of new therapeutic anticancer agents alone or in combination with the classical treatments. The potential use of such NPs against cancer is based on the proapoptotic activity and autophagy, cell growth and metastasis inhibition, and generation of reactive oxygen species as well as radiosensitizing properties described in the studies included in this review. Moreover, we address the different strategies using metal/metal oxide NPs with and without conjugation alone or in combination with radiotherapy or chemotherapy as adjuvants or synergistic agents. NPs obtained from copper, cerium, and zinc were the most studied in various cancer types reported. In many cases, they have been preliminary studies and more research is necessary to increase the knowledge about the therapeutic activity of the metal oxide NPs studied. However, the possibilities that these NPs offer are both extensive and interesting.

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References

  1. Ali D, Alarifi S, Alkahtani S et al (2015) Cerium oxide nanoparticles induce oxidative stress and genotoxicity in human skin melanoma cells. Cell Biochem Biophys 71(3):1643–1651

    Article  CAS  Google Scholar 

  2. Arora S, Tyagi N, Bhardwaj A et al (2015) Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis. Nanomed Nanotechnol 11:1265–1275

    Article  CAS  Google Scholar 

  3. Basu P, Mittal S, Bhadra Vale D, Chami Kharaji Y (2018) Secondary prevention of cervical cancer. Best Pract Res Clin Obstet Gynaecol. https://doi.org/10.1016/j.bpobgyn.2017.08.012

    Article  Google Scholar 

  4. Biplab KC, Paudel SN, Rayamajhi S et al (2016) Enhanced preferential cytotoxicity through surface modification: synthesis, characterization and comparative in vitro evaluation of TritonX-100 modified and unmodified zinc oxide nanoparticles in human breast cancer cell (MDA-MB-231). Chem Cent J 10:16. https://doi.org/10.1186/s13065-016-0162-3

    Article  CAS  Google Scholar 

  5. Bulcke F, Santofimia-Castaño P, Gonzalez-Mateos A et al (2015) Modulation of copper accumulation and copper-induced toxicity by antioxidants and copper chelators in cultured primary brain astrocytes. J Trace Elem Med Biol 32:168–176

    Article  CAS  Google Scholar 

  6. Center M, Jemal A, Lortet-Tieulent J (2012) International variation in prostate cancer incidence and mortality rates. Eur Urol 61:1079–1092

    Article  Google Scholar 

  7. Chattopadhyay S, Dash SK, Tripathy S et al (2015) Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF-α/caspase-8/p38-MAPK signaling in human leukemia cells. J Appl Toxicol 35:603–613

    Article  CAS  Google Scholar 

  8. Chattopadhyay S, Dash SK, Tripathy S et al (2015) Phosphonomethyl iminodiacetic acid-conjugated cobalt oxide nanoparticles liberate Co(++) ion-induced stress associated activation of TNF-α/p38 MAPK/caspase 8-caspase 3 signaling in human leukemia cells. J Biol Inorg Chem 20:123–141

    Article  CAS  Google Scholar 

  9. Chen F, Zhang XH, Hu XD et al (2015) Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells. Int J Nanomed 10:4957–4969

    Article  CAS  Google Scholar 

  10. Condello M, De Berardis B, Ammendolia MG et al (2016) ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells. Toxicol In Vitro 35:169–179

    Article  CAS  Google Scholar 

  11. Cosse JP, Michiels C (2008) Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anti-Cancer Agents Med 8(7):790–797

    Article  CAS  Google Scholar 

  12. Ensign LM, Cone R, Hanes J (2014) Nanoparticle-based drug delivery to the vagina: a review. J Control Release 190:500–514

    Article  CAS  Google Scholar 

  13. Ezhilarasi A, Vijaya JJ, Kaviyarasu K et al (2016) Green synthesis of NiO nanoparticles using Moringa oleifera extract and their biomedical applications: cytotoxicity effect of nanoparticles against HT-29 cancer cells. J Photochem Photobiol B 164:352–360

    Article  CAS  Google Scholar 

  14. Gatta G, Trama A, Capocaccia R (in press) Epidemiology of rare cancers and inequalities in oncologic outcomes. EJSO. https://doi.org/10.1016/j.ejso.2017.08.018

  15. Goodenberger ML, Jenkins RB (2012) Genetics of adult glioma. Cancer Genet 205:613–621

    Article  CAS  Google Scholar 

  16. Hijaz M, Das S, Mert I et al (2016) Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer. BMC Cancer 16:220. https://doi.org/10.1186/s12885-016-2206-4

    Article  CAS  Google Scholar 

  17. Howard D, Garcia-Parra J, Healey GD et al (2016) Antibody–drug conjugates and other nanomedicines: the frontier of gynaecological cancer treatment. Interface Focus 6(6):20160054. https://doi.org/10.1098/rsfs.2016.0054

    Article  Google Scholar 

  18. Jacob JA, Shanmugam A (2015) Silver nanoparticles provoke apoptosis of Dalton’s ascites lymphoma in vivo by mitochondria dependent and independent pathways. Colloid Surf. B 136:1011–1016

    Article  CAS  Google Scholar 

  19. Javed KR, Ahmad M, Ali S et al (2015) Comparison of doxorubicin anticancer drug loading on different metal oxide nanoparticles. Medicine 94(11):e617. https://doi.org/10.1097/MD.0000000000000617

    Article  CAS  Google Scholar 

  20. Jawaid P, Rehman MU, Hassan MA et al (2016) Effect of platinum nanoparticles on cell death induced by ultrasound in human lymphoma U937 cells. Ultrason Sonochem, 206–215

    Article  CAS  Google Scholar 

  21. Jhanwar-Uniyal M, Labagnara M, Friedman M et al (2015) Glioblastoma: molecular pathways, stem cells and therapeutic targets. Cancers 7(2):538–555. https://doi.org/10.3390/cancers7020538 (Basel)

    Article  CAS  Google Scholar 

  22. Jin Y, Ma X, Zhang S et al (2017) A tantalum oxide-based core/shell nanoparticle for triple-modality image-guided chemo-thermal synergetic therapy of esophageal carcinoma. Cancer Lett 397:61–71

    Article  CAS  Google Scholar 

  23. Joshi A, Rastedt W, Faber K et al (2016) Uptake and toxicity of copper oxide nanoparticles in C6 glioma cells. Neurochem Res 41(11):3004–3019

    Article  CAS  Google Scholar 

  24. Khan M, Khan M, Al-Marri AH et al (2016) Apoptosis inducing ability of silver decorated highly reduced graphene oxide nanocomposites in A549 lung cancer. Int J Nanomed 11:873–883

    Article  CAS  Google Scholar 

  25. Khan MI, Mohammad A, Patil G et al (2012) Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. Biomaterials 33:1477–1488

    Article  CAS  Google Scholar 

  26. Khan S, Ansari AA, Khan AA et al (2017) In vitro evaluation of cytotoxicity, possible alteration of apoptotic regulatory proteins, and antibacterial activity of synthesized copper oxide nanoparticles. Colloids Surf B 153:320–326

    Article  CAS  Google Scholar 

  27. Kim JE, Kim H, Soo S et al (2014) In vitro cytotoxicity of SiO2 or ZnO nanoparticles with different sizes and surface charges on U373MG human glioblastoma cells. Int J Nanomed 9(Suppl 2):235–241

    Google Scholar 

  28. Kumar S, Tomar MS, Acharya A (2015) Carboxylic group-induced synthesis and characterization of selenium nanoparticles and its anti-tumor potential on Dalton’s lymphoma cells. Colloid Surf B 126:546–552

    Article  CAS  Google Scholar 

  29. Lehraiki A, Cerezo M, Rouaud F et al (2015) Increased CD271 expression by the NF-kB pathway promotes melanoma cell survival and drives acquired resistance to BRAF inhibitor vemurafenib. Cell Discov 1:15030. https://doi.org/10.1038/celldisc.2015.30. eCollection 2015

  30. Liu P, Jin H, Guo Z et al (2016) Silver nanoparticles outperform gold nanoparticles in radiosensitizing U251 cells in vitro and in an intracranial mouse model of glioma. Int J Nanomed 11:5003–5014

    Article  CAS  Google Scholar 

  31. Manke A, Wang L, Rojanasakul Y (2013) Mechanisms of nanoparticle-induced oxidative stress and toxicity. BioMed Res Int 2013:942916. https://doi.org/10.1155/2013/942916

    Article  CAS  Google Scholar 

  32. Monteiro-Riviere NA, Wiench K, Landsiedel R et al (2011) Safety evaluation of sunscreen formulations containing titanium dioxide and zinc oxide nanoparticles in UVB sunburned skin: an in vitro and in vivo study. Toxicol Sci 123:264–280

    Article  CAS  Google Scholar 

  33. Pandey N, Dhiman S, Srivastava T et al (2016) Transition metal oxide nanoparticles are effective in inhibiting lung cancer cell survival in the hypoxic tumor microenvironment. Chem-Biol Interact 254:221–230

    Article  CAS  Google Scholar 

  34. Pandurangan M, Enkhtaivan G, Kim DH (2016) Anticancer studies of synthesized ZnO nanoparticles against human cervical carcinoma cells. J Photochem Photobio B 158:206–211

    Article  CAS  Google Scholar 

  35. Pandurangan M, Nagajyothi PC, Shim J, Kim DH (2016) Anti-proliferative effect of copper oxide nanorods against human cervical carcinoma cells. Biol Trace Elem Res 173:62–70

    Article  CAS  Google Scholar 

  36. Papis E, Rossi F, Raspanti M et al (2009) Engineered cobalt oxide nanoparticles readily enter cells. Toxicol Lett 189:253–259

    Article  CAS  Google Scholar 

  37. Pešić M, Podolski-Renić A, Stojković S et al (2015) Anti-cancer effects of cerium oxide nanoparticles and its intracellular redox activity. Chem-Biol Interact 232:85–93

    Article  CAS  Google Scholar 

  38. Peynshaert K, Manshian BB, Joris F et al (2014) Exploiting intrinsic nanoparticle toxicity: the pros and cons of nanoparticle-induced autophagy in biomedical research. Chem Rev 114:7581–7609

    Article  CAS  Google Scholar 

  39. Premanathan M, Karthikeyan K, Jeyasubramanian K et al (2011) Selective toxicity of ZnO nanoparticles toward gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomed-Nanotechnol 7:184–192

    Article  CAS  Google Scholar 

  40. Rajan P, Sudbery IM, Eugenia M et al (2014) Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy. Eur Urol 66:32–39

    Article  CAS  Google Scholar 

  41. Raza MH, Siraj S, Arshad A et al (2017) ROS-modulated therapeutic approaches in cancer treatment. J Cancer Res Clin 143(9):1789–1809

    Article  CAS  Google Scholar 

  42. Reichrath J, Rass K (2014) Ultraviolet damage, DNA repair and vitamin D in nonmelanoma skin cancer and in malignant melanoma: an update. Adv Exp Med Biol 810:208–233

    Google Scholar 

  43. Richard S, Saric A, Boucher M (2016) Antioxidative theranostic iron oxide nanoparticles toward brain tumors imaging and ROS production. ACS Chem Biol 11(10):2812–2819

    Article  CAS  Google Scholar 

  44. Rose-James A, Tt S (2012) Molecular markers with predictive and prognostic relevance in lung cancer. Lung Cancer Int 2012:729532. https://doi.org/10.1155/2012/729532

    Article  CAS  Google Scholar 

  45. Sack M, Alili L, Karaman E et al (2014) Combination of conventional chemotherapeutics with redox-active cerium oxide nanoparticles—a novel aspect in cancer therapy. Mol Cancer Ther 13(7):1740–1749

    Article  CAS  Google Scholar 

  46. Safi R, Nelson ER, Chitneni SK et al (2014) Copper signaling axis as a target for prostate cancer therapeutics. Cancer Res 74:5819–5831

    Article  CAS  Google Scholar 

  47. Shafagh M, Rahmani F, Delirezh N (2015) CuO nanoparticles induce cytotoxicity and apoptosis in human K562 cancer cell line via mitochondrial pathway, through reactive oxygen species and P53. Iran J Basic Med Sci 18:993–1000

    Google Scholar 

  48. Simiantonaki N, Jayasinghe C, Michel-Schmidt R et al (2008) Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines. Int J Oncol 32(3):585–592

    CAS  Google Scholar 

  49. Singh AD, Turell ME, Topham AK (2011) Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 118(9):1881–1885

    Article  Google Scholar 

  50. Singh SK, Singh S, Lillard JW Jr et al (2017) Drug delivery approaches for breast cancer. Int J Nanomed 12:6205–6218. https://doi.org/10.2147/IJN.S140325

    Article  Google Scholar 

  51. Song H, Xu Q, Zhu Y et al (2015) Serum adsorption, cellular internalization and consequent impact of cuprous oxide nanoparticles on uveal melanoma cells: implications for cancer therapy. Nanomedicine 10(24):3547–3562

    Article  CAS  Google Scholar 

  52. Stewart C, Konstantinov K, McKinnon S et al (2016) First proof of bismuth oxide nanoparticles as efficient radiosensitisers on highly radioresistant cancer cells. Phys Medica 32:1444–1452

    Article  Google Scholar 

  53. Tuli HS, Kashyap D, Bedi SK et al (2015) Molecular aspects of metal oxide nanoparticle (MO-NPs) mediated pharmacological effects. Life Sci 143:71–79

    Article  CAS  Google Scholar 

  54. Tyagi N, Srivastava SK, Arora S et al (2016) Comparative analysis of the relative potential of silver, zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis. Cancer Lett 383(1):53–61. https://doi.org/10.1016/j.canlet.2016.09.026

    Article  CAS  Google Scholar 

  55. Urruticoechea A, Alemany R, Balart J et al (2010) Recent advances in cancer therapy: an overview. Curr Pharm Design 16(1):3–10

    Article  CAS  Google Scholar 

  56. Vassie JA, Whitelock JM, Lord M (2017) Endocytosis of cerium oxide nanoparticles and modulation of reactive oxygen species in human ovarian and colon cancer cells. Acta Biomater 50:127–141

    Article  CAS  Google Scholar 

  57. Vinardell MP, Mitjans M (2015) Antitumor activities of metal oxide nanoparticles. Nanomaterials 5:1004–1021 Basel

    Article  CAS  Google Scholar 

  58. Vogelsang M, Wilson M, Kirchhoff T (2016) Germline determinants of clinical outcome of cutaneous melanoma. Pigm Cell Melanoma Res 29(1):15–26

    Article  CAS  Google Scholar 

  59. Walsh KM, Ohgaki H, Wrensch MR (2016) Epidemiology. In: Berger MS and Weller M (ed) Handbook of clinical neurology. Elsevier BV, vol 134, pp 3–10

    Google Scholar 

  60. Wang C, Hu X, Gao Y, Ji Y (2015) ZnO nanoparticles treatment induces apoptosis by increasing intracellular ROS levels in LTEP-a-2 cells. Biomed Res Int 2015:423287. https://doi.org/10.1155/2015/423287

    Article  CAS  Google Scholar 

  61. Wang L, Liu Y, Li W et al (2010) Selective targeting of gold nanorods at the mitochondria of cancer cells: implications for cancer therapy. Nano Lett. 11(2):772–780

    Article  CAS  Google Scholar 

  62. Wang Y, Yang F, Zhang HX et al (2013) Cuprous oxide nanoparticles inhibit the growth and metastasis of melanoma by targeting mitochondria. Cell Death Dis 4:e783. https://doi.org/10.1038/cddis.2013.314

    Article  CAS  Google Scholar 

  63. Wang Y, Yang Q-W, Yang Q et al (2017) Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway. Int J Nanomed 12:2569–2579

    Article  CAS  Google Scholar 

  64. Wang Y, Zi X-Y, Su J et al (2012) Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells. Int J Nanomed 7:2641–2652

    CAS  Google Scholar 

  65. Wason MS, Zhao J (2013) Cerium oxide nanoparticles: potential applications for cancer and other diseases. Am J Transl Res 5:126–131

    CAS  Google Scholar 

  66. Wu M, Sun DS, Lin YC et al (2015) Nanodiamonds protect skin from ultraviolet B-induced damage in mice. J Nanobiotechnol 13:35. https://doi.org/10.1186/s12951-015-0094-4

    Article  CAS  Google Scholar 

  67. Wu S, Zhao X, Cui Z et al (2014) Cytotoxicity of graphene oxide and graphene oxide loaded with doxorubicin on human multiple myeloma cells. Int J Nanomed 9:1413–1421

    Google Scholar 

  68. Xia L, Wang Y, Chen Y et al (2017) Cuprous oxide nanoparticles inhibit the growth of cervical carcinoma by inducing autophagy. Oncotarget 8:61083–61092

    Google Scholar 

  69. Xia T, Kovochich M, Liong M et al (2008) Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. ACS Nano 2:2121–2134

    Article  CAS  Google Scholar 

  70. Xiao YF, Li JM, Wang SM et al (2016) Cerium oxide nanoparticles inhibit the migration and proliferation of gastric cancer by increasing DHX15 expression. Int J Nanomed 11:3023–3034

    Article  CAS  Google Scholar 

  71. Yang C, He X, Song L et al (2014) Gamma-Fe2O3 nanoparticles increase therapeutic efficacy of combination with paclitaxel and anti-ABCG2 monoclonal antibody on multiple myeloma cancer stem cells in mouse model. J Biomed Nanotechnol 10:336–344

    Article  CAS  Google Scholar 

  72. Yu B, Wang Y, Yu X (2017) Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells. Int J Nanomed 12:2553–2567

    Article  CAS  Google Scholar 

  73. Zhang W, Qiao L, Wang X et al (2015) Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells. Int J Nanomed 10:3275–3289

    Article  CAS  Google Scholar 

  74. Zhang Y, Yu J, Zhang L et al (2016) Enhanced antitumor effects of doxorubicin on glioma by entrapping in polybutylcyanoacrylate nanoparticles. Tumor Biol 37:2703–2708

    Article  CAS  Google Scholar 

  75. Zijno A, De Angelis I, De Berardis B et al (2015) Different mechanisms are involved in oxidative DNA damage and genotoxicity induction by ZnO and TiO2 nanoparticles in human colon carcinoma cells. Toxicol In Vitro 29(7):1503–1512

    Article  CAS  Google Scholar 

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Vinardell, M.P., Mitjans, M. (2018). Metal/Metal Oxide Nanoparticles for Cancer Therapy. In: Gonçalves, G., Tobias, G. (eds) Nanooncology. Nanomedicine and Nanotoxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-89878-0_10

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