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Biocompatible nano-gallium/hydroxyapatite nanocomposite with antimicrobial activity

  • Biomaterials Synthesis and Characterization
  • Original Research
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Abstract

Intensive research in the area of medical nanotechnology, especially to cope with the bacterial resistance against conventional antibiotics, has shown strong antimicrobial action of metallic and metal-oxide nanomaterials towards a wide variety of bacteria. However, the important remaining problem is that nanomaterials with highest antibacterial activity generally express also a high level of cytotoxicity for mammalian cells. Here we present gallium nanoparticles as a new solution to this problem. We developed a nanocomposite from bioactive hydroxyapatite nanorods (84 wt %) and antibacterial nanospheres of elemental gallium (16 wt %) with mode diameter of 22 ± 11 nm. In direct comparison, such nanocomposite with gallium nanoparticles exhibited better antibacterial properties against Pseudomonas aeruginosa and lower in-vitro cytotoxicity for human lung fibroblasts IMR-90 and mouse fibroblasts L929 (efficient antibacterial action and low toxicity from 0.1 to 1 g/L) than the nanocomposite of hydroxyapatite and silver nanoparticles (efficient antibacterial action and low toxicity from 0.2 to 0.25 g/L). This is the first report of a biomaterial composite with gallium nanoparticles. The observed strong antibacterial properties and low cytotoxicity make the investigated material promising for the prevention of implantation–induced infections that are frequently caused by P. aeruginosa.

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References

  1. Gray F, Kramer DA, Bliss JD. Gallium and Gallium compounds. In: Howe-Grant M, Kirk RE, editors. Kirk-Othmer encyclopedia of chemical technology. 4th edn. New York: John Wiley & Sons; 1998. pp. 158–66.

    Google Scholar 

  2. Greenwood NN, Earnshaw A. Aluminium, Gallium, Indium and Thallium. In: Greenwood NN, Earnshaw A, editors. Chemistry of the elements. 2nd edn. Oxford: Butterworth-Heinemann; 1997. pp. 216–67.

    Google Scholar 

  3. Xu Q, Qudalov N, Guo Q, Jaeger H, Brown E. Effect of oxidation on the mechanical properties of liquid gallium and eutectic gallium-indium. Phys Fluids. 2012;24(6):063101.

    Article  Google Scholar 

  4. Soares BF, MacDonald KF, Fedotov VA, Zheludev NI. Light-induced switching between structural forms with different optical properties in a single gallium nanoparticulate. Nano Lett. 2005;5(10):2104–07.

    Article  Google Scholar 

  5. Parravicini GB, Stella A, Ghigna P, et al. Extreme undercooling (down to 90 K) of liquid metal nanoparticles. Appl Phys Lett. 2006;89:033123.

    Article  Google Scholar 

  6. Knight MW, Coenen T, Yang Y, et al. Gallium plasmonics: deep subwavelength spectroscopic imaging of single and interacting gallium nanoparticles. ACS Nano. 2015;9(2):2049–60.

    Article  Google Scholar 

  7. Bernstein LR. Mechanisms of Therapeutic Activity for Gallium. Pharmacol Rev. 1998;50(4):665–82.

    Google Scholar 

  8. Collery P, Keppler B, Madoulet C, Desoize B. Gallium in cancer treatment. Crit Rev. Oncol Hemat. 2002;42(3):283–96.

    Google Scholar 

  9. Chitambar CR. Medical applications and toxicities of gallium compounds. Int J Environ Res Public Health. 2010;7(5):2337–61.

    Article  Google Scholar 

  10. Kaneko Y, Thoendel M, Olakanmi O, Britigan BE, Singh PK. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J Clin Invest. 2007;117(4):877–88.

    Article  Google Scholar 

  11. Brouqui P, Rousseau MC, Stein A, Drancourt M, Raoult D. Treatment of Pseudomonas aeruginosa-Infected Orthopedic Prostheses with Ceftazidime-Ciprofloxacin Antibiotic Combination. Antimicrob Agents Chemother. 1995;39(11):2423–25.

    Article  Google Scholar 

  12. Sirelkhatim A, Mahmud S, Seeni A, et al. Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano-Micro Lett. 2015;7(3):219–42.

    Article  Google Scholar 

  13. Chernousova S, Epple M. Silver as antibacterial agent: ion, nanoparticle, and metal. Angew Chem Int Edit. 2013;52(6):1636–53.

    Article  Google Scholar 

  14. Seil JT, Webster TJ. Antimicrobial applications of nanotechnology: methods and literature. Int J Nanomed. 2012;7:2767–81.

    Google Scholar 

  15. Dizaj SM, Lotfipour F, Barzegar-Jalali M, Zarrintan MH, Adibkia K. Antimicrobial activity of the metals and metal oxide nanoparticles. Mater Sci Eng C. 2014;44:278–84.

    Article  Google Scholar 

  16. Huh AJ, Kwon YJ. “Nanoantibiotics”: A new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J Control Release. 2011;156(2):128–45.

    Article  Google Scholar 

  17. Dorozhkin SV. Calcium orthophosphates: applications in nature, biology, and medicine. Singapore: Pan Stanford; 2012.

    Book  Google Scholar 

  18. Dorozhkin SV. Calcium orthophosphates in dentistry. J Mater Sci-Mater M. 2013;24(6):1335–63.

    Article  Google Scholar 

  19. Wang P, Zhao L, Liu J, Weir MD, Zhou X, Xu HHK. Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells. Bone Res. 2014;2:14017.

    Google Scholar 

  20. Vukomanović M, Repnik U, Zavašnik-Bergant T, Kostanjšek R, Škapin Srečo D, Suvorov D. Is nano-silver safe within bioactive hydroxyapatite composites? ACS Biomater Sci Eng. 2015;1(10):935–46.

    Article  Google Scholar 

  21. Vukomanović M, Logar M, Škapin SD, Suvorov D. Hydroxyapatite/gold/arginine: designing the structure to create antibacterial activity. J Mater Chem B. 2014;2(11):1557–64.

    Article  Google Scholar 

  22. Repetto G, Peso A. Gallium, Indium, and Thallium. In: Bingham E, Cohrssen B, editors. Patty’s toxicology. 6th edn. New York: John Wiley & Sons; 2012. pp. 257–354.

    Chapter  Google Scholar 

  23. Yu HS, Liao WT. Gallium: Environmental Pollution and Health Effects. In: Nriagu JO, editor. Encyclopedia of environmental health. Burlington: Elsevier; 2011. pp. 829–33.

    Chapter  Google Scholar 

  24. Wataha JC, Nakajima H, Hanks CT, Okabe T. Correlation of cytotoxicity with element release from mercury- and gallium-based dental alloys in vitro. Dent Mater. 1994;10(5):298–303.

    Article  Google Scholar 

  25. Kubásek J, Vojtĕch D, Lipov J, Ruml T. Structure, mechanical properties, corrosion behavior and cytotoxicity of biodegradable Mg-X (X=Sn, Ga, In) alloys. Mater Sci Eng C. 2013;33(4):2421–32.

    Article  Google Scholar 

  26. Wataha JC, Hanks CT, Craig RG. The in vitro effects of metal cations on eukaryotic cell metabolism. J Biomed Mater Res. 1991;25(9):1133–49.

    Article  Google Scholar 

  27. Schedle A, Samorapoompichit P, Rausch-Fan XH, et al. Response of L-929 fibroblasts, human gingival fibroblasts, and human tissue mast cells to various metal cations. J Dent Res. 1995;74(8):1513–20.

    Article  Google Scholar 

  28. Schmalz G, Arenholt-Bindslev D, Pfüller S, Schweikl H. Cytotoxicity of metal cations used in dental cast alloys. ATLA-Altern Lab Anim. 1997;25(3):323–30.

    Google Scholar 

  29. Milheiro A, Nozaki K, Kleverlaan CJ, Muris J, Miura H, Feilzer AJ. In vitro cytotoxicity of metallic ions released from dental alloys. Odontology. 2016;104(2):136–42.

    Article  Google Scholar 

  30. Qiu K, Lin W, Zhou F, et al. Ti-Ga binary alloys developed as potential dental materials. Mater Sci Eng C. 2014;34:474–83.

    Article  Google Scholar 

  31. Lu Y, Hu Q, Lin Y, et al. Transformable liquid-metal nanomedicine. Nat Commun. 2015;6:10066.

    Article  Google Scholar 

  32. Tsai KL, Dye JL. Synthesis, Properties, and characterization of nanometer-size metal particles by homogeneous reduction with alkalides and electrides in aprotic solvents. Chem Mater. 1993;5(13):540–46.

    Article  Google Scholar 

  33. Yarema M, Wörle M, Rossell MD, et al. Monodisperse colloidal gallium nanoparticles: synthesis, low temperature crystallization, surface plasmon resonance and Li-ion storage. J Am Chem Soc. 2014;136:12422–30.

    Article  Google Scholar 

  34. Li YB, Bando Y, Golberg D, Liu ZW. Ga-filled single-crystalline MgO nanotube: Wide-temperature range nanothermometer. Appl Phys Lett. 2003;83(5):999–1001.

    Article  Google Scholar 

  35. Nisoli M, Stagira S, De Silvestri S, et al. Ultrafast electronic dynamics in solid and liquid gallium nanoparticles. Phys Rev Lett. 1997;78(18):3575–78.

    Article  Google Scholar 

  36. Malvezzi AM, Patrini M, Stella A, Tognini P, Cheyssac P, Kofman R. Linear and nonlinear optical characterization of Ga nanoparticle monolayers. Mater Sci Eng C. 2001;15:33–5.

    Article  Google Scholar 

  37. Meléndrez MF, Cárdenas G, Arbiol J. Synthesis and characterization of gallium colloidal nanoparticles. J Colloid Interf Sci. 2010;346(2):279–87.

    Article  Google Scholar 

  38. Han ZH, Yang B, Qi Y, Cumings J. Synthesis of low-melting-point metallic nanoparticles with an ultrasonic nanoemulsion method. Ultrasonics. 2011;51(4):485–8.

    Article  Google Scholar 

  39. Friedman H, Reich S, Popovitz-Biro R, et al. Micro- and nano-spheres of low melting point metals and alloys, formed by ultrasonic cavitation. Ultrason Sonochem. 2013;20(1):432–44.

    Article  Google Scholar 

  40. Kumar VB, Gedanken A, Kimmel G, Porat Z. Ultrasonic cavitation of molten gallium: formation of micro- and nano-spheres. Ultrason Sonochem. 2014;21(3):1166–73.

    Article  Google Scholar 

  41. Yamaguchi A, Mashima Y, Iyoda T. Reversible size control of liquid-metal nanoparticles under ultrasonication. Angew Chem Int Edit. 2015;54:12809–813.

    Article  Google Scholar 

  42. Valappil SP, Ready D, Abou Neel EA, et al. Controlled delivery of antimicrobial gallium ions from phosphate-based glasses. Acta Biomater. 2009;5(4):1198–1210.

    Article  Google Scholar 

  43. Zeimaran E, Pourshahrestani S, Djordjevic I, et al. Antibacterial properties of poly (octanediol citrate)/gallium-containing bioglass composite scaffolds. J Mater Sci-Mater M. 2016;27(1):18.

    Article  Google Scholar 

  44. Sahdev R, Ansari TI, Higham SM, Valappil SP. Potential use of gallium-doped phosphate-based glass material for periodontitis treatment. J Biomater Appl. 2015;30(1):85–92.

    Article  Google Scholar 

  45. Pourshahrestani S, Zeimaran E, Adib Kadri N, et al. Gallium-containing mesoporous bioactive glass with potent hemostatic activity and antibacterial efficacy. J Mater Chem B. 2016;4(1):71–86.

    Article  Google Scholar 

  46. Mellier C, Fayon F, Schnitzler V, et al. Characterization and properties of novel gallium-doped calcium phosphate ceramics. Inorg Chem. 2011;50(17):8252–60.

    Article  Google Scholar 

  47. Mellier C, Fayon F, Boukhechba F, et al. Design and properties of novel gallium-doped injectable apatitic cements. Acta Biomater. 2015;24:322–32.

    Article  Google Scholar 

  48. Jevtić M, Mitrić M, Škapin SD, Jančar B, Ignjatović N, Uskoković D. Crystal structure of hydroxyapatite nanorods synthesized by sonochemical homogeneous precipitation. Cryst Growth Des. 2008;8(7):2217–22.

    Article  Google Scholar 

  49. Miranda M, Fernández A, Díaz M, et al. Silver-hydroxyapatite nanocomposites as bactericidal and fungicidal materials. Int J Mater Res. 2010;101(1):122–27.

    Article  Google Scholar 

  50. Marczenko Z, Balcerzak M. Separation, Pre-concentration and Spectrophotometry in Inorganic Analysis. 1st edn. Amsterdam: Elsevier; 2001.

    Google Scholar 

  51. Miklavič Š, Kogovšek P, Hodnik V, et al. The Pseudomonas aeruginosa RhlR-controlled aegerolysin RahU is a low-affinity rhamnolipidbinding protein. FEMS Microbiol Lett. 2015;362:fnv069.

    Article  Google Scholar 

  52. Wu PC, Kim TH, Brown AS, Losurdo M, Bruno G, Everitt HO. Real-time plasmon resonance tuning of liquid Ga nanoparticles by in situ spectroscopic ellipsometry. Appl Phys Lett. 2007;90(10):103119.

    Article  Google Scholar 

  53. Tsay SF. Relation between the β and rapidly quenched liquid phases of gallium. Phys Rev B. 1994;50(1):103–07.

    Article  Google Scholar 

  54. Bohren C, Huffman DR. Absorption and Scattering of Light by Small Particles. New York: Wiley Interscience; 1998.

    Book  Google Scholar 

  55. Vukomanović M, Bračko I, Poljanšek I, Uskoković D, Škapin SD, Suvorov D. The growth of silver nanoparticles and their combination with hydroxyapatite to form composites via a sonochemical approach. Cryst Growth Des. 2011;11:3802–12.

    Article  Google Scholar 

  56. Takamiya AS, Monteiro DR, Bernabé DG, Gorup LF, Camargo ER, Gomes-Filho JE, Oliveira SHP. In vitro and in vivo toxicity evaluation of colloidal silver nanoparticles used in endodontic treatments. J Endodont. 2016;42(6):953–60.

    Article  Google Scholar 

  57. AshaRani PV, Mun GLK, Hande MP, Valiyaveettil S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano. 2009;3(2):279–90.

    Article  Google Scholar 

  58. Rzhepishevska O, Ekstrand-Hammarström B, Popp M, et al. The antibacterial activity of Ga3+ is influenced by ligand complexation as well as the bacterial carbon source. Antimicrob Agents Ch. 2011;55(12):5568–80.

    Article  Google Scholar 

  59. Bonchi C, Imperi F, Minandri F, Visca P, Frangipani E. Repurposing of gallium-based drugs for antibacterial therapy. BioFactors. 2014;40:303–12.

    Article  Google Scholar 

  60. Durán N, Durán M, de Jesus MB, Seabra AB, Fávaro WJ, Nakazato G. Silver nanoparticles: a new view on mechanistic aspects on antimicrobial activity. Nanomed-Nanotechnol. 2016;12:789–99.

    Article  Google Scholar 

  61. Kora AJ, Arunachalam J. Assessment of antibacterial activity of silver nanoparticles on Pseudomonas Aeruginosa and its mechanism of action. World J Microb Biot. 2011;27(5):1209–16.

    Article  Google Scholar 

  62. Tzitrinovich Z, Lipovsky A, Gedanken A, Lubart R. Visible light-induced OH radicals in Ga2O3: an EPR study. Phys Chem Chem Phys. 2013;15(31):12977–81.

    Article  Google Scholar 

  63. Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Curr Med Chem.. 2005;12(10):1161–208.

    Article  Google Scholar 

  64. Lemire JA, Harrison JJ, Turner RJ. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol. 2013;11(6):371–84.

    Article  Google Scholar 

  65. He W, Zhou YT, Wamer WG, Boudreau MD, Yin JJ. Mechanisms of the pH dependent generation of hydroxyl radicals and oxygen induced by Ag nanoparticles. Biomaterials. 2012;33(30):7547–55.

    Article  Google Scholar 

  66. Bériault R, Hamel R, Chenier D, Mailloux RJ, Joly H, Appanna VD. The overexpression of NADPH-producing enzymes counters the oxidative stress evoked by gallium, an iron mimetic. BioMetals. 2007;20(2):165–76.

    Article  Google Scholar 

  67. Yang M, Chitambar CR. Role of oxidative stress in the induction of metallothionein-2A and heme oxygenase-1 gene expression by the antineoplastic agent gallium nitrate in human lymphoma cells. Free Radical Bio Med. 2008;45(6):763–72.

    Article  Google Scholar 

  68. Sahoo P, Murthy PS, Dhara S, Venugopalan VP, Das A, Tyagi AK. Probing the cellular damage in bacteria induced by GaN nanoparticles using confocal laser Raman spectroscopy. J Nanopart Res. 2013;15:1841.

    Article  Google Scholar 

  69. Kaptay G. On the size and shape dependence of the solubility of nano-particles in solutions. Int J Pharm. 2012;430:253–7.

    Article  Google Scholar 

  70. Reidy B, Haase A, Luch A, Dawson KA, Lynch I. Mechanisms of silver nanoparticle release, transformation and toxicity: a critical review of current knowledge and recommendations for future studies and applications. Materials. 2013;6:2295–350.

    Article  Google Scholar 

  71. Shang L, Nienhaus K, Nienhaus GU. Engineered nanoparticles interacting with cells: size matters. J Nanobiotechnology. 2014;12(5):1–11.

    Google Scholar 

  72. Berhanu D, Valsami-Jones E. Nanotoxicity: are we confident for modelling? - an experimentalist’s point of view. In: Leszczynski J, Puzyn T, editors. Towards efficient designing of safe nanomaterials: innovative merge of computational approaches and experimental techniques. Royal Society of Chemistry; 2012. pp. 54–68.

  73. Glover RD, Miller JM, Hutchison JE. Generation of metal nanoparticles from silver and copper objects: nanoparticle dynamics on surfaces and potential sources of nanoparticles in the environment. ACS Nano. 2011;5(11):8950–7.

    Article  Google Scholar 

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Acknowledgments

The authors appreciate the financial support of the Slovenian Research Agency (financing of young researchers) and the SCOPES (Scientific co-operation between Eastern Europe and Switzerland) project no. IZ73Z0_152327.

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Correspondence to Mario Kurtjak.

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Kurtjak, M., Vukomanović, M., Kramer, L. et al. Biocompatible nano-gallium/hydroxyapatite nanocomposite with antimicrobial activity. J Mater Sci: Mater Med 27, 170 (2016). https://doi.org/10.1007/s10856-016-5777-3

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