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The effects of gold nanoparticles with different surface coatings and sizes on biochemical parameters in mice

Year 2023, Volume: 9 Issue: 1, 131 - 139, 04.01.2023
https://doi.org/10.18621/eurj.998503

Abstract

Objectives: Gold nanoparticles are very popular metallic nanomaterials and they have a wide spectrum of biomedical applications. This study was aimed to the production of stable and monodisperse polyethyleneimine (PEI) and polyethylene glycol (PEG) coated gold nanoparticles (AuNP20 and AuNP50), investigation of their in vivo biochemical effects in the BALB/c mice.

Methods: Gold nanoparticles were synthesized and their surfaces were modified by PEI and PEG. All the necessary physicochemical characterizations were performed. After the single high dose i.v. injection (5 mg Au/kg animal weight) of the AuNP groups, their in vivo biochemical effects were evaluated multiparametrically in the mice on day 14.

Results: Highly monodisperse and stable AuNPs were synthesized successfully. Significant changes in the biochemical hemogram parameters were observed depending on the surface coatings of the AuNPs. PEI and PEG surface coatings increased biocompatibility. No excessive oxidative stress response was observed in all the gold nanoparticle groups.

Conclusions: It has been concluded that the surface chemistry of the particles is a more decisive parameter than the size in terms of in vivo biochemical toxicity. The surface functionalization, stability and biocompatibility of the AuNPs are important parameters for the potential biomedical applications of gold nanoparticles in future studies.

Supporting Institution

The Scientific and Technological Research Council of Turkey (TÜBİTAK)

Project Number

217S135

Thanks

The authors would like to thank the Scientific and Technological Research Council of Turkey (Grant no: 217S135) for providing financial support to this Project.

References

  • 1. Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 2009;38:1759-82.
  • 2. Hameed S, Wang Y, Zhao L, Xie L, Ying Y. Shape-dependent significant physical mutilation and antibacterial mechanisms of gold nanoparticles against foodborne bacterial pathogens (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus) at lower concentrations. Mater Sci Eng C Mater Biol Appl 2020;108:110338.
  • 3. Hamdy ME, Del Carlo M, Hussein HA, Salah TA, El-Deeb AH, Emara MM, et al. Development of gold nanoparticles biosensor for ultrasensitive diagnosis of foot and mouth disease virus. J Nanobiotechnology 2018;16:48.
  • 4. Camilo DE, Miyazaki CM, Shimizu FM, Ferreira M. Improving direct immunoassay response by layer-by-layer films of gold nanoparticles - Antibody conjugate towards label-free detection. Mater Sci Eng C Mater Biol Appl 2019;102:315-23.
  • 5. Kwon SP, Jeon S, Lee SH, Yoon HY, Ryu JH, Choi D, et al. Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging. Biomaterials 2018;150:125-36.
  • 6. Elbakry A, Wurster EC, Zaky A, Liebl R, Schindler E, Bauer-Kreisel P, et al. Layer-by-layer coated gold nanoparticles: size-dependent delivery of DNA into cells. Small 2012;8:3847-56.
  • 7. Perche F, Yi Y, Hespel L, Mi P, Dirisala A, Cabral H, et al. Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity. Biomaterials 2016;90:62-71.
  • 8. Kalimuthu K, Lubin BC, Bazylevich A, Gellerman G, Shpilberg O, Luboshits G, et al. Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells. J Nanobiotechnology 2018;16:34.
  • 9. Ruttala HB, Ramasamy T, Poudel BK, Ruttala RRT, Jin SG, Choi HG, et al. Multi-responsive albumin-lonidamine conjugated hybridized gold nanoparticle as a combined photothermal-chemotherapy for synergistic tumor ablation. Acta Biomater 2020;101:531-43.
  • 10. Hu K, Chen X, Chen W, Zhang L, Li J, Ye J, et al. Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model. Nanomedicine 2018;14:1123-36.
  • 11. Fratoddi I, Venditti I, Cametti C, Russo MV. How toxic are gold nanoparticles? The state-of-the-art. Nano Res 2015;8:1771-99.
  • 12. Brandenberger C, Muhlfeld C, Ali Z, Lenz AG, Schmid O, Parak WJ, et al. Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol-coated gold nanoparticles. Small 2010;6:1669-78.
  • 13. Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 2011;7:1322-37.
  • 14. Wang X, Hu X, Li J, Russe AC, Kawazoe N, Yang Y, et al. Influence of cell size on cellular uptake of gold nanoparticles. Biomater Sci 2016;4:970-8.
  • 15. Stojiljkovic A, Kuehni-Boghenbor K, Gaschen V, Schupbach G, Mevissen M, Kinnear C. et al. High-content analysis of factors affecting gold nanoparticle uptake by neuronal and microglial cells in culture. Nanoscale 2016; 8:6650-16661.
  • 16. Yu M, Lei B, Gao C, Yan J, Ma PX. Optimizing surface-engineered ultra-small gold nanoparticles for highly efficient miRNA delivery to enhance osteogenic differentiation of bone mesenchymal stromal cells. Nano Res 2016;10:49-63.
  • 17. Shahbazi R, Ozcicek I, Ozturk G, Ulubayram K. Functionalized gold nanoparticles manifested as potent carriers for nucleolar targeting. Nanotechnology 2017;28:025103.
  • 18. Ozcicek I, Aysit N, Cakici C, Aydeger A. The effects of surface functionality and size of gold nanoparticles on neuronal toxicity, apoptosis, ROS production and cellular/suborgan biodistribution. Mater Sci Eng C Mater Biol Appl 2021;128:112308.
  • 19. Ozcicek I, Aysit N, Cakici C, Ayturk NU, Aydeger A, Erim UC. The effects of various surface coatings of gold nanorods on toxicity, neuronal localization, microstructural alterations, and in vitro/in vivo biodistribution. Adv Mater Interfaces 2022;9:2101369.
  • 20. Khlebtsov N, Dykman L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev 2011;40:1647-71.
  • 21. Abdelhalim MAK, Jarrar BM. Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration. J Nanobiotechnol 2012;10:5.
  • 22. Turkevich J, Stevenson PC, Hillier J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 1951:11:55
  • 23. Perrault SD, Chan WCW. Synthesis and surface modification of highly monodispersed, spherical gold nanoparticles of 50-200 nm. J Am Chem Soc 2009;131:17042-3.
  • 24. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9.
  • 25. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11.
  • 26. Cho TJ, Gorham JM, Pettibone JM, Liu JY, Tan JJ, V Hackley A. Parallel multiparameter study of PEI-functionalized gold nanoparticle synthesis for biomedical applications: Part 2. Elucidating the role of surface chemistry and polymer structure in performance. Langmuir 2020; 36:14058-69.
  • 27. Shen CC, Hsu SH, Chang KB, Yeh CA, Chang HC, Tang CM, et al. Physical gold nanoparticle-decorated polyethylene glycol-hydroxyapatite composites guide osteogenesis and angiogenesis of mesenchymal stem cells. Biomedicines 2021 9:1632.
  • 28. Katz E. and Willner I. Integrated nanoparticle-biomolecule hybrid systems: Synthesis, properties, and applications. Angew Chem Int Ed Engl 2004;43:6042-108.
  • 29. Ojea-Jimenez I. Puntes V. Instability of cationic gold nanoparticle bioconjugates: the role of citrate ions. J Am Chem Soc 2009;131:13320-7.
  • 30. Song WJ, Du JZ, Sun TM, Zhang PZ, Wang J. Gold nanoparticles capped with polyethyleneimine for enhanced siRNA delivery. Small 2010;6:239-46.
  • 31. Lee Y, Lee SH, Kim JS, Maruyama A, Chen X, Park TG. Controlled synthesis of PEI-coated gold nanoparticles using reductive catechol chemistry for siRNA delivery. J Control Release 2011;155:3-10.
  • 32. Kong L, Qiu J, Sun W, Yang J, Shen M, Wang L, et al. Multifunctional PEI-entrapped gold nanoparticles enable efficient delivery of therapeutic siRNA into glioblastoma cells. Biomater Sci 2017;5:258-66.
  • 33. Shahbazi R, Asik E, Kahraman N, Turk M, Ozpolat B, Ulubayram K. Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer. Nanomedicine 2017;12:1961-73.
  • 34. Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Ramanujam VMS, et al. Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem Bioph Res Co 2010;393:649-55.
  • 35. Ganguly P, Breen A, Pillai SC. Toxicity of nanomaterials: exposure, pathways, assessment, and recent advances. Acs Biomater Sci Eng 2018;4:2237-75.
  • 36. Lopez-Chaves C, Soto-Alvaredo J, Montes-Bayon M, Bettmer J, Llopis J, Sanchez-Gonzalez C. Gold nanoparticles: distribution, bioaccumulation and toxicity. In vitro and in vivo studies. Nanomedicine 2018;14:1-12.
  • 37. Simpson CA, Salleng KJ, Cliffel DE, Feldheim DL. In vivo toxicity, biodistribution, and clearance of glutathione-coated gold nanoparticles. Nanomedicine 2013;9:257-63.
  • 38. Abdoon A.S., Al-Ashkar E.A., Kandil O.M., Shaban A.M., Khaled H.M., El Sayed M.A., et al. Efficacy and toxicity of plasmonic photothermal therapy (PPTT) using gold nanorods (GNRs) against mammary tumors in dogs and cats. Nanomedicine 2016;12:2291-7.
  • 39. Bartneck M, Ritz T, Keul HA, Wambach M, J Bornemann, Gbureck UJ, et al. Peptide-functionalized gold nanorods increase liver injury in hepatitis. Acs Nano 2012;6:8767-77.
  • 40. Fraga S, Brandao A, Soares ME, Morais T, Duarte JA, Pereira L, et al. Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration. Nanomedicine 2014;10:1757-66.
Year 2023, Volume: 9 Issue: 1, 131 - 139, 04.01.2023
https://doi.org/10.18621/eurj.998503

Abstract

Project Number

217S135

References

  • 1. Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. Chem Soc Rev 2009;38:1759-82.
  • 2. Hameed S, Wang Y, Zhao L, Xie L, Ying Y. Shape-dependent significant physical mutilation and antibacterial mechanisms of gold nanoparticles against foodborne bacterial pathogens (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus) at lower concentrations. Mater Sci Eng C Mater Biol Appl 2020;108:110338.
  • 3. Hamdy ME, Del Carlo M, Hussein HA, Salah TA, El-Deeb AH, Emara MM, et al. Development of gold nanoparticles biosensor for ultrasensitive diagnosis of foot and mouth disease virus. J Nanobiotechnology 2018;16:48.
  • 4. Camilo DE, Miyazaki CM, Shimizu FM, Ferreira M. Improving direct immunoassay response by layer-by-layer films of gold nanoparticles - Antibody conjugate towards label-free detection. Mater Sci Eng C Mater Biol Appl 2019;102:315-23.
  • 5. Kwon SP, Jeon S, Lee SH, Yoon HY, Ryu JH, Choi D, et al. Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging. Biomaterials 2018;150:125-36.
  • 6. Elbakry A, Wurster EC, Zaky A, Liebl R, Schindler E, Bauer-Kreisel P, et al. Layer-by-layer coated gold nanoparticles: size-dependent delivery of DNA into cells. Small 2012;8:3847-56.
  • 7. Perche F, Yi Y, Hespel L, Mi P, Dirisala A, Cabral H, et al. Hydroxychloroquine-conjugated gold nanoparticles for improved siRNA activity. Biomaterials 2016;90:62-71.
  • 8. Kalimuthu K, Lubin BC, Bazylevich A, Gellerman G, Shpilberg O, Luboshits G, et al. Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells. J Nanobiotechnology 2018;16:34.
  • 9. Ruttala HB, Ramasamy T, Poudel BK, Ruttala RRT, Jin SG, Choi HG, et al. Multi-responsive albumin-lonidamine conjugated hybridized gold nanoparticle as a combined photothermal-chemotherapy for synergistic tumor ablation. Acta Biomater 2020;101:531-43.
  • 10. Hu K, Chen X, Chen W, Zhang L, Li J, Ye J, et al. Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model. Nanomedicine 2018;14:1123-36.
  • 11. Fratoddi I, Venditti I, Cametti C, Russo MV. How toxic are gold nanoparticles? The state-of-the-art. Nano Res 2015;8:1771-99.
  • 12. Brandenberger C, Muhlfeld C, Ali Z, Lenz AG, Schmid O, Parak WJ, et al. Quantitative evaluation of cellular uptake and trafficking of plain and polyethylene glycol-coated gold nanoparticles. Small 2010;6:1669-78.
  • 13. Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 2011;7:1322-37.
  • 14. Wang X, Hu X, Li J, Russe AC, Kawazoe N, Yang Y, et al. Influence of cell size on cellular uptake of gold nanoparticles. Biomater Sci 2016;4:970-8.
  • 15. Stojiljkovic A, Kuehni-Boghenbor K, Gaschen V, Schupbach G, Mevissen M, Kinnear C. et al. High-content analysis of factors affecting gold nanoparticle uptake by neuronal and microglial cells in culture. Nanoscale 2016; 8:6650-16661.
  • 16. Yu M, Lei B, Gao C, Yan J, Ma PX. Optimizing surface-engineered ultra-small gold nanoparticles for highly efficient miRNA delivery to enhance osteogenic differentiation of bone mesenchymal stromal cells. Nano Res 2016;10:49-63.
  • 17. Shahbazi R, Ozcicek I, Ozturk G, Ulubayram K. Functionalized gold nanoparticles manifested as potent carriers for nucleolar targeting. Nanotechnology 2017;28:025103.
  • 18. Ozcicek I, Aysit N, Cakici C, Aydeger A. The effects of surface functionality and size of gold nanoparticles on neuronal toxicity, apoptosis, ROS production and cellular/suborgan biodistribution. Mater Sci Eng C Mater Biol Appl 2021;128:112308.
  • 19. Ozcicek I, Aysit N, Cakici C, Ayturk NU, Aydeger A, Erim UC. The effects of various surface coatings of gold nanorods on toxicity, neuronal localization, microstructural alterations, and in vitro/in vivo biodistribution. Adv Mater Interfaces 2022;9:2101369.
  • 20. Khlebtsov N, Dykman L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev 2011;40:1647-71.
  • 21. Abdelhalim MAK, Jarrar BM. Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration. J Nanobiotechnol 2012;10:5.
  • 22. Turkevich J, Stevenson PC, Hillier J. A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 1951:11:55
  • 23. Perrault SD, Chan WCW. Synthesis and surface modification of highly monodispersed, spherical gold nanoparticles of 50-200 nm. J Am Chem Soc 2009;131:17042-3.
  • 24. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9.
  • 25. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11.
  • 26. Cho TJ, Gorham JM, Pettibone JM, Liu JY, Tan JJ, V Hackley A. Parallel multiparameter study of PEI-functionalized gold nanoparticle synthesis for biomedical applications: Part 2. Elucidating the role of surface chemistry and polymer structure in performance. Langmuir 2020; 36:14058-69.
  • 27. Shen CC, Hsu SH, Chang KB, Yeh CA, Chang HC, Tang CM, et al. Physical gold nanoparticle-decorated polyethylene glycol-hydroxyapatite composites guide osteogenesis and angiogenesis of mesenchymal stem cells. Biomedicines 2021 9:1632.
  • 28. Katz E. and Willner I. Integrated nanoparticle-biomolecule hybrid systems: Synthesis, properties, and applications. Angew Chem Int Ed Engl 2004;43:6042-108.
  • 29. Ojea-Jimenez I. Puntes V. Instability of cationic gold nanoparticle bioconjugates: the role of citrate ions. J Am Chem Soc 2009;131:13320-7.
  • 30. Song WJ, Du JZ, Sun TM, Zhang PZ, Wang J. Gold nanoparticles capped with polyethyleneimine for enhanced siRNA delivery. Small 2010;6:239-46.
  • 31. Lee Y, Lee SH, Kim JS, Maruyama A, Chen X, Park TG. Controlled synthesis of PEI-coated gold nanoparticles using reductive catechol chemistry for siRNA delivery. J Control Release 2011;155:3-10.
  • 32. Kong L, Qiu J, Sun W, Yang J, Shen M, Wang L, et al. Multifunctional PEI-entrapped gold nanoparticles enable efficient delivery of therapeutic siRNA into glioblastoma cells. Biomater Sci 2017;5:258-66.
  • 33. Shahbazi R, Asik E, Kahraman N, Turk M, Ozpolat B, Ulubayram K. Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer. Nanomedicine 2017;12:1961-73.
  • 34. Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Ramanujam VMS, et al. Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem Bioph Res Co 2010;393:649-55.
  • 35. Ganguly P, Breen A, Pillai SC. Toxicity of nanomaterials: exposure, pathways, assessment, and recent advances. Acs Biomater Sci Eng 2018;4:2237-75.
  • 36. Lopez-Chaves C, Soto-Alvaredo J, Montes-Bayon M, Bettmer J, Llopis J, Sanchez-Gonzalez C. Gold nanoparticles: distribution, bioaccumulation and toxicity. In vitro and in vivo studies. Nanomedicine 2018;14:1-12.
  • 37. Simpson CA, Salleng KJ, Cliffel DE, Feldheim DL. In vivo toxicity, biodistribution, and clearance of glutathione-coated gold nanoparticles. Nanomedicine 2013;9:257-63.
  • 38. Abdoon A.S., Al-Ashkar E.A., Kandil O.M., Shaban A.M., Khaled H.M., El Sayed M.A., et al. Efficacy and toxicity of plasmonic photothermal therapy (PPTT) using gold nanorods (GNRs) against mammary tumors in dogs and cats. Nanomedicine 2016;12:2291-7.
  • 39. Bartneck M, Ritz T, Keul HA, Wambach M, J Bornemann, Gbureck UJ, et al. Peptide-functionalized gold nanorods increase liver injury in hepatitis. Acs Nano 2012;6:8767-77.
  • 40. Fraga S, Brandao A, Soares ME, Morais T, Duarte JA, Pereira L, et al. Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration. Nanomedicine 2014;10:1757-66.
There are 40 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Original Articles
Authors

İlyas Özçiçek 0000-0002-4495-7395

Çağrı Çakıcı 0000-0002-8662-5284

Neşe Ayşit 0000-0002-4243-9092

Ümit Can Erim 0000-0002-4121-588X

Project Number 217S135
Publication Date January 4, 2023
Submission Date September 21, 2021
Acceptance Date April 26, 2022
Published in Issue Year 2023 Volume: 9 Issue: 1

Cite

AMA Özçiçek İ, Çakıcı Ç, Ayşit N, Erim ÜC. The effects of gold nanoparticles with different surface coatings and sizes on biochemical parameters in mice. Eur Res J. January 2023;9(1):131-139. doi:10.18621/eurj.998503

e-ISSN: 2149-3189 


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