Phytosynthesized metal oxide nanoparticles for pharmaceutical applications

  • Swetha Andra
  • Satheesh Kumar Balu
  • Jaison Jeevanandham
  • Murugesan Muthalagu
  • Manisha Vidyavathy
  • Yen San Chan
  • Michael Kobina DanquahEmail author


Developments in nanotechnology field, specifically, metal oxide nanoparticles have attracted the attention of researchers due to their unique sensing, electronic, drug delivery, catalysis, optoelectronics, cosmetics, and space applications. Physicochemical methods are used to fabricate nanosized metal oxides; however, drawbacks such as high cost and toxic chemical involvement prevail. Recent researches focus on synthesizing metal oxide nanoparticles through green chemistry which helps in avoiding the involvement of toxic chemicals in the synthesis process. Bacteria, fungi, and plants are the biological sources that are utilized for the green nanoparticle synthesis. Due to drawbacks such as tedious maintenance and the time needed for the nanoparticle formation, plant extracts are widely used in nanoparticle production. In addition, plants are available all over the world and phytosynthesized nanoparticles show comparatively less toxicity towards mammalian cells. Secondary metabolites including flavonoids, terpenoids, and saponins are present in plant extracts, and these are highly responsible for nanoparticle formation and reduction of toxicity. Hence, this article gives an overview of recent developments in the phytosynthesis of metal oxide nanoparticles and their toxic analysis in various cells and animal models. Also, their possible mechanism in normal and cancer cells, pharmaceutical applications, and their efficiency in disease treatment are also discussed.


Pharmaceutical applications Cytotoxicity In vitro analysis Metal oxide nanoparticles Phytochemicals 



The authors would like to acknowledge their respective departments for their support in writing this article.

Author contribution

SA, SKB, and JJ wrote the manuscript which was revised and reviewed by MKD, YSC, MM, and MV. All authors read and approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abrahamson WG, Caswell H (1982) On the comparative allocations of biomass, energy, and nutrients in plants. Ecology 63(4):982–991Google Scholar
  2. Ahamed M, Khan MM, Akhtar MJ, Alhadlaq HA, Alshamsan A (2017) Ag-doping regulates the cytotoxicity of TiO 2 nanoparticles via oxidative stress in human cancer cells. Sci Rep 7(1):17662Google Scholar
  3. Akram MW, Fakhar-e-Alam M, Atif M, Butt AR, Asghar A, Jamil Y, Alimgeer K, Wang ZM (2018) In vitro evaluation of the toxic effects of MgO nanostructure in Hela cell line. Sci Rep 8(1):4576Google Scholar
  4. Alaraby M, Annangi B, Hernández A, Creus A, Marcos R (2015) A comprehensive study of the harmful effects of ZnO nanoparticles using Drosophila melanogaster as an in vivo model. J Hazard Mater 296:166–174Google Scholar
  5. Alaraby M, Hernández A, Marcos R (2017) Copper oxide nanoparticles and copper sulphate act as antigenotoxic agents in drosophila melanogaster. Environ Mol Mutagen 58(1):46–55Google Scholar
  6. Ali A, Hira Zafar MZ, ul Haq I, Phull AR, Ali JS, Hussain A (2016) Synthesis, characterization, applications, and challenges of iron oxide nanoparticles. Nanotechnol Sci Appl 9:49–67Google Scholar
  7. Al-Shabib NA, Husain FM, Hassan I, Khan MS, Ahmed F, Qais FA, Oves M, Rahman M, Khan RA, Khan A (2018) Biofabrication of zinc oxide nanoparticle from Ochradenus baccatus leaves: broad-spectrum antibiofilm activity, protein binding studies, and in vivo toxicity and stress studies. J Nanomater 2018:1–14Google Scholar
  8. Alwi R, Telenkov S, Mandelis A, Leshuk T, Gu F, Oladepo S, Michaelian K (2012) Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics. Biomed Opt Express 3(10):2500–2509Google Scholar
  9. Amiri M, Etemadifar Z, Daneshkazemi A, Nateghi M (2017) Antimicrobial effect of copper oxide nanoparticles on some oral bacteria and candida species. J Dent Biomater 4(1):347–352Google Scholar
  10. Ann LC, Mahmud S, Seeni A, Bakhori SKM, Sirelkhatim A, Mohamad D, Hasan H (2015) Structural morphology and in vitro toxicity studies of nano- and micro-sized zinc oxide structures. J Environ Chem Eng 3(1):436–444. Google Scholar
  11. Ansari M, Kurian GA (2017) Differential effect of aqueous Desmodium gangeticum root extract mediated TiO2 nanoparticles on isolated mitochondria, cells and Wistar rats. Asian Pac J Trop Biomed 7(11):1031–1035Google Scholar
  12. Antoine TE, Hadigal SR, Yakoub AM, Mishra YK, Bhattacharya P, Haddad C, Valyi-Nagy T, Adelung R, Prabhakar BS, Shukla D (2016) Intravaginal zinc oxide tetrapod nanoparticles as novel immunoprotective agents against genital herpes. J Immunol 196:4566–4575Google Scholar
  13. Arciniegas-Grijalba P, Patiño-Portela M, Mosquera-Sánchez L, Guerrero-Vargas J, Rodríguez-Páez J (2017) ZnO nanoparticles (ZnO-NPs) and their antifungal activity against coffee fungus Erythricium salmonicolor. Appl Nanosci 7(5):225–241Google Scholar
  14. Aruoma OI (1998) Free radicals, oxidative stress, and antioxidants in human health and disease. J Am Oil Chem Soc 75(2):199–212Google Scholar
  15. Ashokan AP, Paulpandi M, Dinesh D, Murugan K, Vadivalagan C, Benelli G (2017) Toxicity on dengue mosquito vectors through Myristica fragrans-synthesized zinc oxide Nanorods, and their cytotoxic effects on liver cancer cells (HepG2). J Clust Sci 28(1):205–226. Google Scholar
  16. Ashraf JM, Ansari MA, Fatma S, Abdullah SM, Iqbal J, Madkhali A, Hamali AH, Ahmad S, Jerah A, Echeverria V (2018) Inhibiting effect of zinc oxide nanoparticles on advanced glycation products and oxidative modifications: a potential tool to counteract oxidative stress in neurodegenerative diseases. Mol Neurobiol:1–15Google Scholar
  17. Assadian E, Zarei MH, Gilani AG, Farshin M, Degampanah H, Pourahmad J (2018) Toxicity of copper oxide (CuO) nanoparticles on human blood lymphocytes. Biol Trace Elem Res 184(2):350–357. Google Scholar
  18. Bala N, Saha S, Chakraborty M, Maiti M, Das S, Basu R, Nandy P (2015) Green synthesis of zinc oxide nanoparticles using Hibiscus subdariffa leaf extract: effect of temperature on synthesis, anti-bacterial activity and anti-diabetic activity. RSC Adv 5(7):4993–5003Google Scholar
  19. Balas M, Ciobanu CS, Burtea C, Stan MS, Bezirtzoglou E, Predoi D, Dinischiotu A (2017) Synthesis, characterization, and toxicity evaluation of dextran-coated iron oxide nanoparticles. Metals 7(2):63Google Scholar
  20. Banumathi B, Malaikozhundan B, Vaseeharan B (2016) Invitro acaricidal activity of ethnoveterinary plants and green synthesis of zinc oxide nanoparticles against Rhipicephalus (Boophilus) microplus. Vet Parasitol 216:93–100Google Scholar
  21. Begletsova NN, Shinkarenko OA, Chumakov AS, Al-Alwani AJ, Selifonov AA, Selifonova EI, Pozharov MV, Zakharevich AM,Chernova RK, Kolesnikova AS, Glukhovskoy EG (2017) Copper nanoparticles obtained by chemical reduction stabilized by micelles of various surfactants. J Phys Conf Ser 917(9)Google Scholar
  22. Boisselier E, Astruc D (2009) Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 38(6):1759–1782Google Scholar
  23. Burns J, Yokota T, Ashihara H, Lean ME, Crozier A (2002) Plant foods and herbal sources of resveratrol. J Agric Food Chem 50(11):3337–3340Google Scholar
  24. Chang Y-N, Zhang M, Xia L, Zhang J, Xing G (2012) The toxic effects and mechanisms of CuO and ZnO nanoparticles. Materials 5(12):2850–2871Google Scholar
  25. Cohen Y, Rallo R, Liu R, Liu HH (2012) In silico analysis of nanomaterials hazard and risk. Acc Chem Res 46(3):802–812Google Scholar
  26. Czajka M, Sawicki K, Sikorska K, Popek S, Kruszewski M, Kapka-Skrzypczak L (2015) Toxicity of titanium dioxide nanoparticles in central nervous system. Toxicol in Vitro 29(5):1042–1052Google Scholar
  27. Daehler CC (1998) The taxonomic distribution of invasive angiosperm plants: ecological insights and comparison to agricultural weeds. Biol Conserv 84(2):167–180Google Scholar
  28. Das RK, Brar SK, Verma M (2016) Checking the biocompatibility of plant-derived metallic nanoparticles: molecular perspectives. Trends Biotechnol 34(6):440–449Google Scholar
  29. Davatgaran-Taghipour Y, Masoomzadeh S, Farzaei MH, Bahramsoltani R, Karimi-Soureh Z, Rahimi R, Abdollahi M (2017) Polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective. Int J Nanomedicine 12:2689–2702Google Scholar
  30. Dey A, Manna S, Chattopadhyay S, Mondal D, Chattopadhyay D, Raj A, Das S, Bag BG, Roy S (2018) Azadirachta indica leaves mediated green synthesized copper oxide nanoparticles induce apoptosis through activation of TNF-α and caspases signaling pathway against cancer cells. J Saudi Chem Soc 23:222–238. Google Scholar
  31. Dillard CJ, German JB (2000) Phytochemicals: nutraceuticals and human health. J Sci Food Agric 80(12):1744–1756Google Scholar
  32. Dizaj SM, Lotfipour F, Barzegar-Jalali M, Zarrintan MH, Adibkia K (2014) Antimicrobial activity of the metals and metal oxide nanoparticles. Mater Sci Eng Proc Conf 44:278–284. Google Scholar
  33. Dobrucka R, Dlugaszewska J, Kaczmarek M (2018) Cytotoxic and antimicrobial effects of biosynthesized ZnO nanoparticles using of Chelidonium majus extract. Biomed Microdevices 20(1):5Google Scholar
  34. Durán N, Durán M, de Jesus MB, Seabra AB, Fávaro WJ, Nakazato G (2016) Silver nanoparticles: a new view on mechanistic aspects on antimicrobial activity. Nanomedicine: NBM 12(3):789–799Google Scholar
  35. Eriksson P, Tal AA, Skallberg A, Brommesson C, Hu Z, Boyd RD, Olovsson W, Fairley N, Abrikosov IA, Zhang X (2018) Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement. Sci Rep 8(1):6999Google Scholar
  36. Farré G, Sanahuja G, Naqvi S, Bai C, Capell T, Zhu C, Christou P (2010) Travel advice on the road to carotenoids in plants. Plant Sci 179(1–2):28–48Google Scholar
  37. Gandhi PR, Jayaseelan C, Kamaraj C, Rajasree SR, Mary RR (2018) In vitro antimalarial activity of synthesized TiO2 nanoparticles using Momordica charantia leaf extract against Plasmodium falciparum. J Appl Biomed 16:378–386Google Scholar
  38. George S, Gardner H, Seng EK, Chang H, Wang C, Yu Fang CH, Richards M, Valiyaveettil S, Chan WK (2014) Differential effect of solar light in increasing the toxicity of silver and titanium dioxide nanoparticles to a fish cell line and zebrafish embryos. Environ Sci Technol 48(11):6374–6382Google Scholar
  39. Gopi D, Kanimozhi K, Kavitha L (2015) Opuntia ficus indica peel derived pectin mediated hydroxyapatite nanoparticles: synthesis, spectral characterization, biological and antimicrobial activities. Spectrochim Acta A 141:135–143Google Scholar
  40. Groiss S, Selvaraj R, Varadavenkatesan T, Vinayagam R (2017) Structural characterization, antibacterial and catalytic effect of iron oxide nanoparticles synthesised using the leaf extract of Cynometra ramiflora. J Mol Struct 1128:572–578Google Scholar
  41. Guozhong C (2004) Nanostructures and nanomaterials: synthesis, properties and applications. World Scientific, SingaporeGoogle Scholar
  42. Hariharan D, Srinivasan K, Nehru LC (2017) Synthesis and characterization of Tio2 nanoparticles using Cynodon dactylon leaf extract for antibacterial and anticancer (A549 cell lines) activity. J Nanomed Res 5(6):00138Google Scholar
  43. He F, Yu W, Fan X, Jin B (2017) In vitro cytotoxicity of biosynthesized titanium dioxide nanoparticles in human prostate cancer cell lines. Trop J Pharm Res 16(12):2793–2799Google Scholar
  44. Hola K, Markova Z, Zoppellaro G, Tucek J, Zboril R (2015) Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances. Biotechnol Adv 33(6):1162–1176Google Scholar
  45. Hossain SS, Zhang Y, Liang X, Hussain F, Ferrari M, Hughes TJ, Decuzzi P (2013) In silico vascular modeling for personalized nanoparticle delivery. Nanomedicine 8(3):343–357Google Scholar
  46. Hua J, Vijver MG, Richardson MK, Ahmad F, Peijnenburg WJ (2014) Particle-specific toxic effects of differently shaped zinc oxide nanoparticles to zebrafish embryos (Danio rerio). Environ Toxicol Chem 33(12):2859–2868Google Scholar
  47. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Psychiatry 55(3):181–184Google Scholar
  48. Hussain SM, Braydich-Stolle LK, Schrand AM, Murdock RC, Yu KO, Mattie DM, Schlager JJ, Terrones M (2009) Toxicity evaluation for safe use of nanomaterials: recent achievements and technical challenges. Adv Mater 21(16):1549–1559Google Scholar
  49. Imran Din M, Rani A (2016) Recent advances in the synthesis and stabilization of nickel and nickel oxide nanoparticles: a green adeptness. Int J Anal Chem 2016:1–14Google Scholar
  50. Iravani S (2011) Green synthesis of metal nanoparticles using plants. Green Chem 13(10):2638–2650Google Scholar
  51. Izadiyan Z, Shameli K, Miyake M, Hara H, Mohamad SEB, Kalantari K, Taib SHM, Rasouli E (2018) Cytotoxicity assay of plant-mediated synthesized iron oxide nanoparticles using Juglans regia green husk extract. Arab J Chem.
  52. Jasim NO (2015) Antifungal activity of Zinc oxide nanoparticles on Aspergillus fumigatus fungus & Candida albicans yeast. Citeseer 5:23–28Google Scholar
  53. Jeevanandam J (2017) Enhanced synthesis and delivery of magnesium oxide nanoparticles for reverse insulin resistance in type 2 diabetes mellitus. Curtin University, BentleyGoogle Scholar
  54. Jeevanandam J, Chan YS, Danquah MK (2016) Biosynthesis of metal and metal oxide nanoparticles. ChemBioEng Rev 3(2):55–67. Google Scholar
  55. Jeevanandam J, Aing YS, Chan YS, Pan S, Danquah MK (2017a) Nanoformulation and application of phytochemicals as antimicrobial agents. In: Antimicrobial Nanoarchitectonics. Elsevier, pp 61–82Google Scholar
  56. Jeevanandam J, Chan YS, Danquah MK (2017b) Calcination-dependent morphology transformation of sol-gel-synthesized MgO nanoparticles. ChemistrySelect 2(32):10393–10404Google Scholar
  57. Jeevanandam J, San Chan Y, Danquah MK (2017c) Biosynthesis and characterization of MgO nanoparticles from plant extracts via induced molecular nucleation. New J Chem 41(7):2800–2814Google Scholar
  58. Jeevanandam J, San Chan Y, Ku YH (2018) Aqueous Eucalyptus globulus leaf extract-mediated biosynthesis of MgO nanorods. Appl Biol Chem 61(2):197–208Google Scholar
  59. Jeevanandam J, Chan YS, Danquah MK (2019) Effect of pH variations on morphological transformation of biosynthesized MgO nanoparticles. Part Sci Technol:1–14.
  60. Jeong S-W, Kim H (2014) Filtration of fullerene and copper oxide nanoparticles using surface-modified microfilters. Environ Monit Assess 186(9):5855–5864. Google Scholar
  61. Ji W, Zhu D, Chen Y, Hu J, Li F (2017) In-vitro cytotoxicity of biosynthesized Zinc oxide nanoparticles towards cardiac cell lines of Catla catla. Biomed Res 28(5):2262–2266Google Scholar
  62. Kahani SA, Yagini Z (2014) A comparison between chemical synthesis magnetite nanoparticles and biosynthesis magnetite. Bioinorg Chem Appl 2014:1–7Google Scholar
  63. Keller AA, Wang H, Zhou D, Lenihan HS, Cherr G, Cardinale BJ, Miller R, Ji Z (2010) Stability and aggregation of metal oxide nanoparticles in natural aqueous matrices. Environ Sci Technol 44(6):1962–1967. Google Scholar
  64. Kennedy DO, Wightman EL (2011) Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr 2(1):32–50Google Scholar
  65. Kominkova M, Milosavljevic V, Vitek P, Polanska H, Cihalova K, Dostalova S, Hynstova V, Guran R, Kopel P, Richtera L (2017) Comparative study on toxicity of extracellularly biosynthesized and laboratory synthesized CdTe quantum dots. J Biotechnol 241:193–200Google Scholar
  66. Kumar B, Smita K (2016) Phytochemically functionalized silver and gold nanoparticles to treat microbes, viruses and cancer. In: Ranjan S, Dasgupta N, Lichtfouse E (eds) Nanoscience in food and agriculture 2. Springer International Publishing, Cham, pp 235–252. Google Scholar
  67. Kumar P, Senthamil Selvi S, Lakshmi Prabha A, Prem Kumar K, Ganeshkumar RS, Govindaraju M (2012) Synthesis of silver nanoparticles from Sargassum tenerrimum and screening phytochemicals for its antibacterial activity. Nano Biomed Eng 4(1):12–16Google Scholar
  68. Kumari P, Panda PK, Jha E, Kumari K, Nisha K, Mallick MA, Verma SK (2017) Mechanistic insight to ROS and apoptosis regulated cytotoxicity inferred by green synthesized CuO nanoparticles from Calotropis gigantea to embryonic zebrafish. Sci Rep 7(1):16284Google Scholar
  69. Labowsky M, Lowenthal J, Fahmy TM (2015) An in silico analysis of nanoparticle/cell diffusive transfer: application to nano-artificial antigen-presenting cell: t-cell interaction. Nanomedicine: NBM 11(4):1019–1028Google Scholar
  70. Lammers T, Aime S, Hennink WE, Storm G, Kiessling F (2011) Theranostic nanomedicine. Acc Chem Res 44(10):1029–1038Google Scholar
  71. Lau IP, Chen H, Wang J, Ong HC, Leung KCF, Ho HP, Kong SK (2012) In vitro effect of CTAB-and PEG-coated gold nanorods on the induction of eryptosis/erythroptosis in human erythrocytes. Nanotoxicology 6(8):847–856Google Scholar
  72. Lee W-H, Loo C-Y, Young PM, Traini D, Mason RS, Rohanizadeh R (2014) Recent advances in curcumin nanoformulation for cancer therapy. Expert Opin Drug Deliv 11(8):1183–1201Google Scholar
  73. Lindsley DL, Grell EH (1968) Genetic variations of Drosophila melanogaster. Carnegie Inst.. 1968;627. Washington Publication. CiNii article ID (NAID) - 10006700069Google Scholar
  74. Ling D, Lee N, Hyeon T (2015) Chemical synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications. Acc Chem Res 48(5):1276–1285Google Scholar
  75. Liu J, Peng L, Huang W, Li Z, Pan J, Sang L, Lu S, Zhang J, Li W, Luo Y (2017) Balancing between aging and cancer: molecular genetics meets traditional Chinese medicine. J Cell Biochem 118(9):2581–2586Google Scholar
  76. Lotfian H, Nemati F (2016) Cytotoxic effect of tio2 nanoparticles on breast cancer cell line (MCF-7). IIOAB J 7:219–224Google Scholar
  77. Magro M, Baratella D, Bonaiuto E, de A Roger J, Vianello F (2018) New perspectives on biomedical applications of iron oxide nanoparticles. Curr Med Chem 25(4):540–555Google Scholar
  78. Majeed S, Danish M, Muhadi NFBB (2018) Genotoxicity and apoptotic activity of biologically synthesized magnesium oxide nanoparticles against human lung cancer A-549 cell line. Adv Nat Sci Nanosci Nanotechnol 9(2):025011Google Scholar
  79. Mansouri B, Maleki A, Johari SA, Reshahmanish N (2015) Effects of cobalt oxide nanoparticles and cobalt ions on gill histopathology of zebrafish (Danio rerio). AACL Bioflux 8(3):438–444Google Scholar
  80. Marella S, Tollamadugu NVKVP (2018) Nanotechnological approaches for the development of herbal drugs in treatment of diabetes mellitus–a critical review. IET Nanobiotechnol 12:549–556Google Scholar
  81. Mashitah MD, San Chan Y, Jason J (2016) Antimicrobial properties of nanobiomaterials and the mechanism. In: Nanobiomaterials in antimicrobial therapy. Elsevier, Amsterdam, pp 261–312Google Scholar
  82. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and down syndrome. Proc Natl Acad Sci 82(12):4245–4249Google Scholar
  83. Meigen JW, Loew H (1824) Systematische Beschreibung der bekannten europäischen zweiflügeligen Insekten, vol 4. FW Forstmann, AachenGoogle Scholar
  84. Mishra PK, Mishra H, Ekielski A, Talegaonkar S, Vaidya B (2017) Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discov Today 22(12):1825–1834. Google Scholar
  85. Mostafa AA (2015) Antibacterial activity of zinc oxide nanoparticles against toxigenic Bacillus cereus and Staphylococcus aureus isolated from some Egyptian food. Int J 6(2):145–154Google Scholar
  86. Mukherjee P, Ahmad A, Mandal D, Senapati S, Sainkar SR, Khan MI, Parishcha R, Ajaykumar PV, Alam M, Kumar R, Sastry M (2001) Fungus-mediated synthesis of silver nanoparticles and their immobilization in the mycelial matrix: a novel biological approach to nanoparticle synthesis. Nano Lett 1(10):515–519. Google Scholar
  87. Murali M, Suganthi P, Athif P, Bukhari AS, Mohamed HS, Basu H, Singhal R (2017) Histological alterations in the hepatic tissues of Al2O3 nanoparticles exposed freshwater fish Oreochromis mossambicus. J Trace Elem Med Biol 44:125–131Google Scholar
  88. Nagajyothi P, Cha SJ, Yang IJ, Sreekanth T, Kim KJ, Shin HM (2015) Antioxidant and anti-inflammatory activities of zinc oxide nanoparticles synthesized using Polygala tenuifolia root extract. J Photochem Photobiol B 146:10–17Google Scholar
  89. Nagajyothi P, Pandurangan M, Kim DH, Sreekanth T, Shim J (2017) Green synthesis of iron oxide nanoparticles and their catalytic and in vitro anticancer activities. J Clust Sci 28(1):245–257Google Scholar
  90. Namvar F, Rahman HS, Mohamad R, Baharara J, Mahdavi M, Amini E, Chartrand MS, Yeap SK (2014) Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract. Int J Nanomedicine 9:2479Google Scholar
  91. Nankar RP, Raman M, Doble M (2016) Nanoformulations of polyphenols for prevention and treatment of cardiovascular and metabolic disorders. In: Emulsions. Elsevier, pp 107–151Google Scholar
  92. Narasaiah P, Mandal BK, Sarada N (2017) Biosynthesis of copper oxide nanoparticles from Drypetes sepiaria leaf extract and their catalytic activity to dye degradation. In: IOP conference series: materials science and engineering, vol 2. IOP Publishing, p 022012Google Scholar
  93. Narayanan KB, Sakthivel N (2010) Biological synthesis of metal nanoparticles by microbes. Adv Colloid Interf Sci 156(1):1–13. Google Scholar
  94. Ng CT, Yong LQ, Hande MP, Ong CN, Yu LE, Bay BH, Baeg GH (2017) Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster. Int J Nanomedicine 12:1621–1637Google Scholar
  95. Nijveldt RJ, Van Nood E, Van Hoorn DE, Boelens PG, Van Norren K, Van Leeuwen PA (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74(4):418–425Google Scholar
  96. Niu N, Wang L (2015) In vitro human cell line models to predict clinical response to anticancer drugs. Pharmacogenomics 16(3):273–285Google Scholar
  97. Padil VVT, Černík M (2013) Green synthesis of copper oxide nanoparticles using gum karaya as a biotemplate and their antibacterial application. Int J Nanomedicine 8:889Google Scholar
  98. Park CJ, Song SH, Kim DH, Gye MC (2016) Developmental and acute toxicity of cetylpyridinium chloride in Bombina orientalis (Amphibia: Anura). Aquat Toxicol 177:446–453Google Scholar
  99. Patel SB, Baker N, Marques I, Hamlekhan A, Mathew MT, Takoudis C, Friedrich C, Sukotjo C, Shokuhfar T (2017) Transparent TiO2 nanotubes on zirconia for biomedical applications. RSC Adv 7(48):30397–30410. Google Scholar
  100. Patra N, Dehury N, Pal A, Behera A, Patra S (2018) Preparation and mechanistic aspect of natural xanthone functionalized gold nanoparticle. Mater Sci Eng, Proc Conf 90:439–445Google Scholar
  101. Peterson RD, Chen W, Cunningham BT, Andrade JE (2015) Enhanced sandwich immunoassay using antibody-functionalized magnetic iron-oxide nanoparticles for extraction and detection of soluble transferrin receptor on a photonic crystal biosensor. Biosens Bioelectron 74:815–822Google Scholar
  102. Prashanth G, Prashanth P, Bora U, Gadewar M, Nagabhushana B, Ananda S, Krishnaiah G, Sathyananda H (2015) In vitro antibacterial and cytotoxicity studies of ZnO nanopowders prepared by combustion assisted facile green synthesis. Karbala Int J Mod Sci 1(2):67–77Google Scholar
  103. Rajakumar G, Rahuman AA, Roopan SM, Chung I-M, Anbarasan K, Karthikeyan V (2015) Efficacy of larvicidal activity of green synthesized titanium dioxide nanoparticles using Mangifera indica extract against blood-feeding parasites. Parasitol Res 114(2):571–581Google Scholar
  104. Rajakumar G, Thiruvengadam M, Mydhili G, Gomathi T, Chung I-M (2018) Green approach for synthesis of zinc oxide nanoparticles from Andrographis paniculata leaf extract and evaluation of their antioxidant, anti-diabetic, and anti-inflammatory activities. Bioprocess Biosyst Eng 41(1):21–30Google Scholar
  105. Rajeshkumar S, Kumar SV, Ramaiah A, Agarwal H, Lakshmi T, Roopan SM (2018) Biosynthesis of zinc oxide nanoparticles using Mangifera indica leaves and evaluation of their antioxidant and cytotoxic properties in lung cancer (A549) cells. Enzym Microb Technol 117:91–95. Google Scholar
  106. Ramanathan AA, Aqra MW (2019) An overview of the green road to the synthesis of nanoparticles. J Mater Sci Res Rev:1–11Google Scholar
  107. Ramírez Prada D, Delgado G, Hidalgo Patino C, Perez-Navero J, Gil Campos M (2011) Using of WHO guidelines for the management of severe malnutrition to cases of marasmus and kwashiorkor in a Colombia children’s hospital. Nutr Hosp 26(5)Google Scholar
  108. Ratheesh G, Tian L, Venugopal JR, Ezhilarasu H, Sadiq A, Fan T-P, Ramakrishna S (2017) Role of medicinal plants in neurodegenerative diseases. Biomanufacturing Reviews 2(1):2Google Scholar
  109. Reddy LS, Nisha MM, Joice M, Shilpa P (2014) Antimicrobial activity of zinc oxide (ZnO) nanoparticle against Klebsiella pneumoniae. Pharm Biol 52(11):1388–1397Google Scholar
  110. Reddy GD, Noorjahan M, Mangatayaru KG, Krishnakanth M (2018) Microwave assisted phytosynthesis and characterization of magnetic iron oxide quantum dots using Moringa oleifera. Mater Sci Res India 15(2):145–150Google Scholar
  111. Rehana D, Mahendiran D, Kumar RS, Rahiman AK (2017) Evaluation of antioxidant and anticancer activity of copper oxide nanoparticles synthesized using medicinally important plant extracts. Biomed Pharmacother 89:1067–1077Google Scholar
  112. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414(6859):105–111Google Scholar
  113. Robards K (2003) Strategies for the determination of bioactive phenols in plants, fruit and vegetables. J Chromatogr A 1000(1–2):657–691Google Scholar
  114. Sabir S, Arshad M, Chaudhari SK (2014) Zinc oxide nanoparticles for revolutionizing agriculture: synthesis and applications. Sci World J 2014:1–8Google Scholar
  115. Saif S, Tahir A, Asim T, Chen Y (2016) Plant mediated green synthesis of CuO nanoparticles: comparison of toxicity of engineered and plant mediated CuO nanoparticles towards Daphnia magna. Nanomaterials 6(11):205Google Scholar
  116. Saikia J, Yazdimamaghani M, Hadipour Moghaddam SP, Ghandehari H (2016) Differential protein adsorption and cellular uptake of silica nanoparticles based on size and porosity. ACS Appl Mater Interfaces 8(50):34820–34832. Google Scholar
  117. Sankar R, Dhivya R, Shivashangari KS, Ravikumar V (2014) Wound healing activity of Origanum vulgare engineered titanium dioxide nanoparticles in Wistar Albino rats. J Mater Sci Mater Med 25(7):1701–1708Google Scholar
  118. Saranya S, Vijayaranai K, Pavithra S, Raihana N, Kumanan K (2017) In vitro cytotoxicity of zinc oxide, iron oxide and copper nanopowders prepared by green synthesis. Toxicol Rep 4:427–430Google Scholar
  119. Sathishkumar G, Logeshwaran V, Sarathbabu S, Jha PK, Jeyaraj M, Rajkuberan C, Senthilkumar N, Sivaramakrishnan S (2018) Green synthesis of magnetic Fe3O4 nanoparticles using Couroupita guianensis Aubl. fruit extract for their antibacterial and cytotoxicity activities. Artif Cells Nanomed Biotechnol 46(3):589–598Google Scholar
  120. Sawada Y, Nakabayashi R, Yamada Y, Suzuki M, Sato M, Sakata A, Akiyama K, Sakurai T, Matsuda F, Aoki T (2012) RIKEN tandem mass spectral database (ReSpect) for phytochemicals: a plant-specific MS/MS-based data resource and database. Phytochemistry 82:38–45Google Scholar
  121. Scaffidi P, Misteli T (2005) Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11(4):440–445Google Scholar
  122. Schmidt H (2001) Nanoparticles by chemical synthesis, processing to materials and innovative applications. Appl Organomet Chem 15(5):331–343. Google Scholar
  123. Selvakumar S, Gangatharan S, Rao M (2016) Preliminary phytochemical screening of root extracts of Crossandra infundibuliformis. Res J Pharm Technol 9(2):131Google Scholar
  124. Senthilkumar S, Rajendran A (2018) Biosynthesis of TiO 2 nanoparticles using Justicia gendarussa leaves for photocatalytic and toxicity studies. Res Chem Intermed:1–18Google Scholar
  125. Shah M, Fawcett D, Sharma S, Tripathy S, Poinern G (2015) Green synthesis of metallic nanoparticles via biological entities. Materials 8(11):7278–7308Google Scholar
  126. Shaker AM, Zaki AH, Abdel-Rahim EF, Khedr MH (2016) Novel CuO nanoparticles for pest management and pesticides photodegradation. Adv Environ Biol 10(12):274–283Google Scholar
  127. Sharma A, Cornejo C, Mihalic J, Geyh A, Bordelon DE, Korangath P, Westphal F, Gruettner C, Ivkov R (2018) Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles. Sci Rep 8(1):4916Google Scholar
  128. Shi L-B, Tang P-F, Zhang W, Zhao Y-P, Zhang L-C, Zhang H (2017) Green synthesis of CuO nanoparticles using Cassia auriculata leaf extract and in vitro evaluation of their biocompatibility with rheumatoid arthritis macrophages (RAW 264.7). Trop J Pharm Res 16(1):185–192Google Scholar
  129. Siddique YH, Haidari M, Khan W, Fatima A, Jyoti S, Khanam S, Naz F, Rahul AF, Singh BR (2015) Toxic potential of copper-doped ZnO nanoparticles in Drosophila melanogaster (Oregon R). Toxicol Mech Methods 25(6):425–432Google Scholar
  130. Singh S, Kumar N, Kumar M, Jyoti, Agarwal A, Mizaikoff B (2017) Electrochemical sensing and remediation of 4-nitrophenol using bio-synthesized copper oxide nanoparticles. Chem Eng J 313:283–292. Google Scholar
  131. Singh A, Singh NB, Afzal S, Singh T, Hussain I (2018) Zinc oxide nanoparticles: a review of their biological synthesis, antimicrobial activity, uptake, translocation and biotransformation in plants. J Mater Sci 53(1):185–201. Google Scholar
  132. Sirelkhatim A, Mahmud S, Seeni A, Kaus NHM, Ann LC, Bakhori SKM, Hasan H, Mohamad D (2015) Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nanomicro Lett 7(3):219–242Google Scholar
  133. Sivaraj R, Rahman PK, Rajiv P, Narendhran S, Venckatesh R (2014) Biosynthesis and characterization of Acalypha indica mediated copper oxide nanoparticles and evaluation of its antimicrobial and anticancer activity. Spectrochim Acta A 129:255–258Google Scholar
  134. Song Y, Yang J (2016) Preparation and in-vitro cytotoxicity of zinc oxide nanoparticles against osteoarthritic chondrocytes. Trop J Pharm Res 15(11):2321–2327Google Scholar
  135. Sood K, Kaur J, Khatri M (2017) Comparative neurotoxicity evaluation of zinc oxide nanoparticles by crawling assay on Drosophila melanogaster. International Journal of Engineering Technology Science and Research (IJETSR) 4(4):440–444Google Scholar
  136. Sridhar R, Ravanan S, Venugopal JR, Sundarrajan S, Pliszka D, Sivasubramanian S, Gunasekaran P, Prabhakaran M, Madhaiyan K, Sahayaraj A (2014) Curcumin-and natural extract-loaded nanofibres for potential treatment of lung and breast cancer: in vitro efficacy evaluation. J Biomater Sci Polym Ed 25(10):985–998Google Scholar
  137. Srivastava V, Gusain D, Sharma YC (2015) Critical review on the toxicity of some widely used engineered nanoparticles. Ind Eng Chem Res 54(24):6209–6233Google Scholar
  138. Strähle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S, Schumacher A, Selderslaghs I, Weiss C, Witters H (2012) Zebrafish embryos as an alternative to animal experiments—a commentary on the definition of the onset of protected life stages in animal welfare regulations. Reprod Toxicol 33(2):128–132Google Scholar
  139. Sugirtha P, Divya R, Yedhukrishnan R, Suganthi K, Anusha N, Ponnusami V, Rajan K (2015) Green synthesis of magnesium oxide nanoparticles using Brassica oleracea and Punica granatum peels and their anticancer and photocatalytic activity. Asian J Chem 27(7):2513–2517Google Scholar
  140. Sulaiman GM, Tawfeeq AT, Jaaffer MD (2018) Biogenic synthesis of copper oxide nanoparticles using olea europaea leaf extract and evaluation of their toxicity activities: an in vivo and in vitro study. Biotechnol Prog 34(1):218–230Google Scholar
  141. Suman TY, Ravindranath RRS, Elumalai D, Kaleena PK, Ramkumar R, Perumal P, Aranganathan L, Chitrarasu PS (2015) Larvicidal activity of titanium dioxide nanoparticles synthesized using Morinda citrifolia root extract against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus and its other effect on non-target fish. Asian Pac J Trop Dis 5(3):224–230Google Scholar
  142. Suresh J, Pradheesh G, Alexramani V, Sundrarajan M, Hong SI (2018a) Green synthesis and characterization of zinc oxide nanoparticle using insulin plant (Costus pictus D. Don) and investigation of its antimicrobial as well as anticancer activities. Adv Nat Sci Nanosci Nanotechnol 9(1):015008Google Scholar
  143. Suresh J, Pradheesh G, Alexramani V, Sundrarajan M, Hong SI (2018b) Green synthesis and characterization of hexagonal shaped MgO nanoparticles using insulin plant (Costus pictus D. Don) leave extract and its antimicrobial as well as anticancer activity. Adv Powder Technol 29(7):1685–1694Google Scholar
  144. Sutradhar P, Saha M, Maiti D (2014) Microwave synthesis of copper oxide nanoparticles using tea leaf and coffee powder extracts and its antibacterial activity. J Nanostruct Chem 4(1):86Google Scholar
  145. Tagliabracci VS, Girard JM, Segvich D, Meyer C, Turnbull J, Zhao X, Minassian BA, DePaoli-Roach AA, Roach PJ (2008) Abnormal metabolism of glycogen phosphate as a cause for Lafora disease. J Biol Chem 283(49):33816–33825Google Scholar
  146. Talib WH, Mahasneh AM (2010) Antimicrobial, cytotoxicity and phytochemical screening of Jordanian plants used in traditional medicine. Molecules 15(3):1811–1824Google Scholar
  147. Tammina SK, Mandal BK, Ranjan S, Dasgupta N (2017) Cytotoxicity study of Piper nigrum seed mediated synthesized SnO2 nanoparticles towards colorectal (HCT116) and lung cancer (A549) cell lines. J Photochem Photobiol B 166:158–168. Google Scholar
  148. Taze C, Panetas I, Kalogiannis S, Feidantsis K, Gallios GP, Kastrinaki G, Konstandopoulos AG, Václavíková M, Ivanicova L, Kaloyianni M (2016) Toxicity assessment and comparison between two types of iron oxide nanoparticles in Mytilus galloprovincialis. Aquat Toxicol 172:9–20Google Scholar
  149. Thakkar KN, Mhatre SS, Parikh RY (2010) Biological synthesis of metallic nanoparticles. Nanomedicine: NBM 6(2):257–262. Google Scholar
  150. Thakur P, Joshi SS (2012) Effect of alcohol and alcohol/water mixtures on crystalline structure of CdS nanoparticles. J Exp Nanosci 7(5):547–558. Google Scholar
  151. Thatoi P, Kerry RG, Gouda S, Das G, Pramanik K, Thatoi H, Patra JK (2016) Photo-mediated green synthesis of silver and zinc oxide nanoparticles using aqueous extracts of two mangrove plant species, Heritiera fomes and Sonneratia apetala and investigation of their biomedical applications. J Photochem Photobiol B 163:311–318. Google Scholar
  152. Tholl D (2015) Biosynthesis and biological functions of terpenoids in plants. In: Biotechnology of isoprenoids. Springer, Berlin, pp 63–106Google Scholar
  153. Tinkle S, McNeil SE, Mühlebach S, Bawa R, Borchard G, Barenholz Y, Tamarkin L, Desai N (2014) Nanomedicines: addressing the scientific and regulatory gap. Ann N Y Acad Sci 1313(1):35–56. Google Scholar
  154. Van Hoecke K, De Schamphelaere KAC, Van der Meeren P, Smagghe G, Janssen CR (2011) Aggregation and ecotoxicity of CeO2 nanoparticles in synthetic and natural waters with variable pH, organic matter concentration and ionic strength. Environ Pollut 159(4):970–976Google Scholar
  155. Verma A, Stellacci F (2010) Effect of surface properties on nanoparticle–cell interactions. Small 6(1):12–21Google Scholar
  156. Vicario-Parés U, Castañaga L, Lacave JM, Oron M, Reip P, Berhanu D, Valsami-Jones E, Cajaraville MP Orbea A(2014) Comparative toxicity of metal oxide nanoparticles (CuO, ZnO and TiO 2) to developing zebrafish embryos. J Nanopart Res 16(8):2550Google Scholar
  157. Vimala K, Sundarraj S, Paulpandi M, Vengatesan S, Kannan S (2014) Green synthesized doxorubicin loaded zinc oxide nanoparticles regulates the Bax and Bcl-2 expression in breast and colon carcinoma. Process Biochem 49(1):160–172Google Scholar
  158. Williams M, Waters E, Golbek M, Wormington J (2015) Effect of different shades of light on photosynthesis. JIBI 2(4)Google Scholar
  159. Wu D, Cederbaum AI (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 27:277–284Google Scholar
  160. Yang Y, Yu C (2016) Advances in silica based nanoparticles for targeted cancer therapy. Nanomedicine: NBM 12(2):317–332. Google Scholar
  161. Yew YP, Shameli K, Miyake M, Ahmad Khairudin NBB, Mohamad SEB, Naiki T, Lee KX (2018) Green biosynthesis of superparamagnetic magnetite Fe3O4 nanoparticles and biomedical applications in targeted anticancer drug delivery system: a review. Arab J Chem.
  162. Yugandhar P, Vasavi T, Devi PUM, Savithramma N (2017) Bioinspired green synthesis of copper oxide nanoparticles from Syzygium alternifolium (Wt.) Walp: characterization and evaluation of its synergistic antimicrobial and anticancer activity. Appl Nanosci 7(7):417–427Google Scholar
  163. Zhang Y, Zhang C, Liu K, Zhu X, Liu F, Ge X (2018a) Biologically synthesized titanium oxide nanostructures combined with morphogenetic protein as wound healing agent in the femoral fracture after surgery. J Photochem Photobiol B 182:35–41. Google Scholar
  164. Zhang T, Duan X, Zhan M, Min X (2018b) Purification, preliminary structural characterization and in vitro antioxidant activity of polysaccharides from Camellia japonica pollen. J Chem Soc Pak 40(3)Google Scholar
  165. Zhao Y, Li C, Chen M, Yu X, Chang Y, Chen A, Zhu H, Tang Z (2016) Growth of aligned ZnO nanowires via modified atmospheric pressure chemical vapor deposition. Phys Lett A 380(47):3993–3997Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Textile TechnologyAnna UniversityChennaiIndia
  2. 2.Department of Ceramic TechnologyAnna UniversityChennaiIndia
  3. 3.Department of Chemical Engineering, Faculty of Engineering and ScienceCurtin UniversityMiriMalaysia
  4. 4.Chemical Engineering DepartmentUniversity of TennesseeChattanoogaUSA

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