Ag2WO4 nanoparticles radiolabeled with technetium-99m: a potential new tool for tumor identification and uptake

  • Carla Júnia Santos
  • Francisco Moura Filho
  • Fernanda Lapa Campos
  • Carolina de Aguiar Ferreira
  • André Luís Branco de Barros
  • Daniel Crístian Ferreira SoaresEmail author


Silver tungstate nanoparticles have been presenting attractive characteristics that could allow its usage in the biomedical sciences. In this study, Ag2WO4 nanoparticles with an average size of 242 nm were obtained and radiolabeled with technetium-99m with high labeling-yield as well as high stability. Biodistribution studies were carried out in healthy and tumor-bearing mice to determine the nanoparticle’s in vivo behavior. The results revealed an important tumor-to-muscle ratio, reaching values above than 1.5, demonstrated the ability of this nanomaterial in accumulating preferentially in tumor tissue. All results together, converge to consider the Ag2WO4 nanoparticles as a potential system against cancer and a potential new radiolabeled probe for tumor identification and uptake.


[99mTc]–Ag2WO4 nanoparticles Ag2WO4 tumor probe Ag2WO4 tumor-bearing mice biodistribution 



The authors would like to thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP): (01.13.0343.02), Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) and Rede Mineira de Química for the financial support.


  1. 1.
    Jain J, Arora S, Rajwade JM et al (2009) Silver nanoparticles in therapeutics: development of an antimicrobial gel formulation for topical use. Mol Pharm 6:1388–1401. CrossRefPubMedGoogle Scholar
  2. 2.
    Kalishwaralal K, BarathManiKanth S, Pandian SRK et al (2010) Silver nano—a trove for retinal therapies. J Control Release 145:76–90. CrossRefPubMedGoogle Scholar
  3. 3.
    Byod A, Natuurkunde T, Hogeschool T, Delft CJ (1982) The polymorphism of silver tungstate Ag2WO4. J Appl Crystallogr 820:10114–10116Google Scholar
  4. 4.
    Haro Chávez NL, de Avila ED, Barbugli PA et al (2018) Promising effects of silver tungstate microcrystals on fibroblast human cells and three dimensional collagen matrix models: a novel non-cytotoxic material to fight oral disease. Colloids Surfaces B Biointerfaces 170:505–513. CrossRefPubMedGoogle Scholar
  5. 5.
    Pereira PFS, Santos CC, Gouveia AF et al (2017) α-Ag2–2 x Znx WO4 (0 ≤ x ≤ 0.25) solid solutions: structure, morphology, and optical properties. Inorg Chem 56:7360–7372. CrossRefPubMedGoogle Scholar
  6. 6.
    Lin Z, Li J, Zheng Z et al (2015) Electronic reconstruction of α-Ag2 WO4 nanorods for visible-light photocatalysis. ACS Nano 9:7256–7265. CrossRefPubMedGoogle Scholar
  7. 7.
    Cavalcante LS, Almeida MAP, Avansi W et al (2012) Cluster coordination and photoluminescence properties of alpha-Ag2WO4 microcrystals. Inorg Chem 51:10675–10687CrossRefGoogle Scholar
  8. 8.
    De Santana YVB, Gomes JEC, Matos L et al (2014) Silver molybdate and silver tungstate nanocomposites with enhanced photoluminescence. Nanomater Nanotechnol 4:22. CrossRefGoogle Scholar
  9. 9.
    Pinatti IM, Nogueira IC, Pereira WS et al (2015) Structural and photoluminescence properties of Eu 3+ doped α-Ag2 WO4 synthesized by the green coprecipitation methodology. Dalton Trans 44:17673–17685. CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang R, Cui H, Yang X et al (2012) Facile hydrothermal synthesis and photocatalytic activity of rod-like nanosized silver tungstate. Micro Nano Lett 7:1285–1288. CrossRefGoogle Scholar
  11. 11.
    Chen H, Xu Y (2014) Photoactivity and stability of Ag2WO4 for organic degradation inaqueous suspensions. Appl Surf Sci 319:319–323. CrossRefGoogle Scholar
  12. 12.
    Cabral AC, Cavalcante LS, Deus RC et al (2014) Photoluminescence properties of praseodymium doped cerium oxide nanocrystals. Ceram Int 40:4445–4453. CrossRefGoogle Scholar
  13. 13.
    Longo E, Volanti DP, Longo VM et al (2014) Toward an understanding of the growth of Ag filaments on α-Ag2 WO4 and their photoluminescent properties: a combined experimental and theoretical study. J Phys Chem C 118:1229–1239. CrossRefGoogle Scholar
  14. 14.
    Aguir K, Mastelaro VR, Longo E (2014) A novel ozone gas sensor based on one-dimensional (1D) α-Ag2 WO4 nanostructures. Nanoscale. CrossRefPubMedGoogle Scholar
  15. 15.
    Da Silva LF, Longo E, Catto AC et al (2016) Acetone gas sensor based on α-Ag2WO4 nanorods obtained via a microwave-assisted hydrothermal route. J Alloys Compd 683:186–190. CrossRefGoogle Scholar
  16. 16.
    Longo VM, De Foggi CC, Ferrer MM et al (2014) Potentiated electron transference in α-Ag2WO4 microcrystals with Ag nanofilaments as microbial agent. J Phys Chem A 118:5769–5778. CrossRefPubMedGoogle Scholar
  17. 17.
    Foggi CC, Fabbro MT, Santos LPS et al (2017) Synthesis and evaluation of Α-Ag2WO4 as novel antifungal agent. Chem Phys Lett 674:125–129. CrossRefGoogle Scholar
  18. 18.
    Roca RA, Sczancoski JC, Nogueira IC et al (2015) Facet-dependent photocatalytic and antibacterial properties of α-Ag2 WO4 crystals: combining experimental data and theoretical insights. Catal Sci Technol 5:4091–4107. CrossRefGoogle Scholar
  19. 19.
    Selvamani M, Krishnamoorthy G, Ramadoss M et al (2016) Ag@Ag8W4O16nanoroasted rice beads with photocatalytic, antibacterial and anticancer activity. Mater Sci Eng, C 60:109–118. CrossRefGoogle Scholar
  20. 20.
    Santos CJ, Ferreira Soares DC, de Ferreira CdeA et al (2018) Antiangiogenic evaluation of ZnWO4 nanoparticles synthesised through microwave-assisted hydrothermal method. J Drug Target. CrossRefPubMedGoogle Scholar
  21. 21.
    Maier-Hauff K, Ulrich F, Nestler D et al (2011) Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neurooncol 103:317–324. CrossRefPubMedGoogle Scholar
  22. 22.
    Beik J, Abed Z, Ghoreishi FS et al (2016) Nanotechnology in hyperthermia cancer therapy: from fundamental principles to advanced applications. J Control Release 235:205–221. CrossRefPubMedGoogle Scholar
  23. 23.
    Ingham B, Toney MF (2014) X-ray diffraction for characterizing metallic films. Met Film Electron Opt Magn Appl. CrossRefGoogle Scholar
  24. 24.
    Monteiro LOF, Fernandes RS, Oda CMR et al (2018) Biomedicine & Pharmacotherapy Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system : a biodistribution study. Biomed Pharmacother 97:489–495. CrossRefPubMedGoogle Scholar
  25. 25.
    Oda CMR, Fernandes RS, de Araújo Lopes SC et al (2017) Synthesis, characterization and radiolabeling of polymeric nano-micelles as a platform for tumor delivering. Biomed Pharmacother 89:268–275. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Soares DCF, Cardoso VN, de Barros ALB et al (2012) Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing (159)Gd-DTPA-BMA in Ehrlich tumor bearing mice. Eur J Pharm Sci 45:58–64. CrossRefPubMedGoogle Scholar
  27. 27.
    Bilecka I, Niederberger M (2010) Microwave chemistry for inorganic nanomaterials synthesis. Nanoscale 2:1358. CrossRefPubMedGoogle Scholar
  28. 28.
    Perreux L, Loupy A (2001) A tentative rationalization of microwave effects in organic synthesis according to the reaction medium, and mechanistic considerations. Tetrahedron 57:9199–9223. CrossRefGoogle Scholar
  29. 29.
    Gedye R, Smith F, Westaway K et al (1986) The use of microwave ovens for rapid organic synthesis. Tetrahedron Lett 27:279–282. CrossRefGoogle Scholar
  30. 30.
    Giguere RJ, Bray TL, Duncan SM, Majetich G (1986) Application of commercial microwave ovens to organic synthesis. Tetrahedron Lett 27:4945–4948. CrossRefGoogle Scholar
  31. 31.
    Righettoni M, Tricoli A, Pratsinis SE (2010) Si:WO3 sensors for highly selective detection of acetone for easy diagnosis of diabetes by breath analysis. Anal Chem 82:3581–3587. CrossRefPubMedGoogle Scholar
  32. 32.
    Kim DH, Shim YS, Jeon JM et al (2014) Vertically ordered hematite nanotube array as an ultrasensitive and rapid response acetone sensor. ACS Appl Mater Interfaces 6:14779–14784. CrossRefPubMedGoogle Scholar
  33. 33.
    Muthamizh S, Giribabu K, Manigandan R, Praveen Kumar S, Munusamy S, Suresh R, Narayanan V (2016) Ag@Ag8W4O16 nanoroasted rice beads with photocatalytic, antibacterial and anticancer activity. Mater Sci Eng C 60(1):109–118Google Scholar
  34. 34.
    Pinatti IM, Fern GR, Longo E et al (2019) Luminescence properties of α-Ag2WO4 nanorods co-doped with Li + and Eu3 + cations and their effects on its structure. J Lumin 206:442–454. CrossRefGoogle Scholar
  35. 35.
    He H, Xue S, Wu Z et al (2016) Synthesis and characterization of robust Ag2S/Ag2WO4 composite microrods with enhanced photocatalytic performance. J Mater Res 31:2598–2607. CrossRefGoogle Scholar
  36. 36.
    Turkovič A, Fox DL, Scott JF et al (1977) High temperature Raman spectroscopy of silver tetratungstate, Ag8W4O16. Mater Res Bull 12:189–195. CrossRefGoogle Scholar
  37. 37.
    Basiev T, Sobol A, Voronko Y, Zverev P (2000) Spontaneous Raman spectroscopy of tungstate and molybdate crystals for Raman lasers. Opt Mater (Amst) 15:205–216. CrossRefGoogle Scholar
  38. 38.
    Ernsting MJ, Murakami M, Roy A, Li S-DD (2013) Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. J Control Release 172:782–794. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Raza K, Kumar P, Kumar N, Malik R (2017) Pharmacokinetics and biodistribution of the nanoparticles. Adv Nanomedicine Deliv Ther Nucleic Acids. CrossRefGoogle Scholar
  40. 40.
    De Barros ALB, De Oliveira Ferraz KS, Dantas TCS et al (2015) Synthesis, characterization, and biodistribution studies of 99mTc-labeled SBA-16 mesoporous silica nanoparticles. Mater Sci Eng, C 56:181–188. CrossRefGoogle Scholar
  41. 41.
    Psimadas D, Bouziotis P, Georgoulias P et al (2013) Radiolabeling approaches of nanoparticles with 99mTc. Contrast Media Mol Imaging 8:333–339. CrossRefPubMedGoogle Scholar
  42. 42.
    Snehalatha M, Venugopal K, Saha RN et al (2008) Etoposide loaded PLGA and PCL nanoparticles II: biodistribution and pharmacokinetics after radiolabeling with Tc-99m. Drug Deliv 15:277–287. CrossRefPubMedGoogle Scholar
  43. 43.
    Psimadas D, Baldi G, Ravagli C et al (2012) Preliminary evaluation of a 99mTc labeled hybrid nanoparticle bearing a cobalt ferrite core: in vivo biodistribution. J Biomed Nanotechnol 8:575–585CrossRefGoogle Scholar
  44. 44.
    Fu CM, Wang YF, Chao YC et al (2004) Directly labeling ferrite nanoparticles with Tc-99m radioisotope for diagnostic applications. IEEE Trans Magn 40:3003–3005. CrossRefGoogle Scholar
  45. 45.
    Wang AY, Kuo CL, Lin JL et al (2010) Study of magnetic ferrite nanoparticles labeled with 99mTc-pertechnetate. J Radioanal Nucl Chem 284:405–413. CrossRefGoogle Scholar
  46. 46.
    Meng Y, Zhang X-H, Du B-Y et al (2011) Thermosets with core–shell nanodomain by incorporation of core crosslinked star polymer into epoxy resin. Polymer (Guildf) 52:391–399. CrossRefGoogle Scholar
  47. 47.
    Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cnacer chemotherapy: mechanism of tumoritropic accumulatio of proteins and the antitumor agents Smancs. Cancer Res 46:6387–6392. CrossRefPubMedGoogle Scholar
  48. 48.
    Heneweer C, Holland JP, Divilov V et al (2011) Magnitude of enhanced permeability and retention effect in tumors with different phenotypes: 89Zr-albumin as a model system. J Nucl Med 52:625. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  • Carla Júnia Santos
    • 1
  • Francisco Moura Filho
    • 1
  • Fernanda Lapa Campos
    • 2
  • Carolina de Aguiar Ferreira
    • 3
  • André Luís Branco de Barros
    • 2
  • Daniel Crístian Ferreira Soares
    • 1
    Email author
  1. 1.Laboratório de BioengenhariaUniversidade Federal de ItajubáItabiraBrazil
  2. 2.Faculdade de FarmáciaUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  3. 3.Department of Biomedical EngineeringUniversity of Wisconsin-MadisonMadisonUSA

Personalised recommendations