Synthesis, characterization, and toxicity of hollow gold nanoshells

  • Sayma Adriana Rodriguez-Montelongo
  • Jesus Gonzalez-Hernandez
  • Abel Hurtado Macias
  • Ana Sonia Silva-Ramirez
  • Claudia G. Castillo Martin del Campo
  • Jose Manuel Gutierrez-Hernandez
  • Facundo Ruiz
  • Omar Gonzalez-OrtegaEmail author
Research Paper


Hollow gold nanoshells (HGN) with a diameter of 50–70 nm and tunable optical properties within the near-infrared region were synthesized from a substitution reaction using a sacrificial template, in which the morphological properties of the HGN were affected by the synthesis conditions. Using EDX line scan, the composition of the structure was determined to verify if the sacrificial template is completely consumed or residues remain after the chemical synthesis, obtaining that the final HGN structure contains about 11% of the remaining silver that showed no significant effect on the cell viability of a hNS1 cell line, but resulted as toxic on a C6 glioma cell line at high concentrations. The photothermal properties were evaluated using a NIR laser, which despite its low power showed the conversion of light into heat. This study was conducted to evaluate the potential of these nanostructures as therapeutic agents with an emphasis on toxicity.


Photothermal therapy Hollow gold nanoshells Surface plasmon resonance EDX line scan Toxicity Silver residues 


Funding information

This work was funded by “Fondo de Apoyo a la Investigacion, UASLP” (C14-FAI-04-23.23) and by “Fondo Sectorial de Investigacion para la Educacion, CONACYT” (CB-258444-2016).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abdollahi SN, Naderi M, Amoabediny G (2013) Synthesis and characterization of hollow gold nanoparticles using silica spheres as templates. Colloids Surf A Physicochem Eng Asp 436:1069–1075. CrossRefGoogle Scholar
  2. Allabashi R, Stach W, De La Escosura-Muñiz A et al (2009) ICP-MS: a powerful technique for quantitative determination of gold nanoparticles without previous dissolving. J Nanopart Res 11:2003–2011. CrossRefGoogle Scholar
  3. Au L, Zheng D, Zhou F, Li ZY, Li X, Xia Y (2008) A quantitative study on the photothermal effect of immuno gold nanocages targeted to breast cancer cells. ACS Nano 2:1645–1652. CrossRefGoogle Scholar
  4. Bardhan R, Lal S, Joshi A, Halas NJ (2011) Theranostic nanoshells: from probe design to imaging and treatment of cancer. Acc Chem Res 44:936–946. CrossRefGoogle Scholar
  5. Chen J, Wiley B, Li ZY, Campbell D, Saeki F, Cang H, Au L, Lee J, Li X, Xia Y (2005) Gold nanocages: engineering their structure for biomedical applications. Adv Mater 17:2255–2261. CrossRefGoogle Scholar
  6. Chen J, Glaus C, Laforest R, Zhang Q, Yang M, Gidding M, Welch MJ, Xia Y (2010) Gold nanocages as photothermal transducers for cancer treatment. Small 6:811–817. CrossRefGoogle Scholar
  7. Chien CC, Cheng CC, Chen HH, Hwu Y, Chu YS, Petibois C, Chen A, Ching YT, Margaritondo G (2012) X-ray microscopy and tomography detect the accumulation of bare and PEG-coated gold nanoparticles in normal and tumor mouse tissues. Anal Bioanal Chem 404:1287–1296CrossRefGoogle Scholar
  8. Doan N, Kontturi K, Johans C (2010) Directing oxidation of cobalt nanoparticles with the capping ligand. J Colloid Interface Sci 350:126–131. CrossRefGoogle Scholar
  9. Gabudean AM, Lerouge F, Gallavardin T, Iosin M, Zaiba S, Maury O, Baldeck PL, Andraud C, Parola S (2011) Synthesis and optical properties of dyes encapsulated in gold hollow nanoshells. Opt Mater (Amst) 33:1377–1381. CrossRefGoogle Scholar
  10. Han C, Yang J, Gu J (2018) Immobilization of silver nanoparticles in Zr-based MOFs: induction of apoptosis in cancer cells. J Nanopart Res 20.
  11. Hao E, Li SY, Bailey RC, Zou S, Schatz GC, Hupp JT (2004) Optical properties of metal nanoshells. J Phys Chem B 108:1224–1229. CrossRefGoogle Scholar
  12. Huang X, El-Sayed MA (2011) Plasmonic photo-thermal therapy (PPTT). Alex J Med 47:1–9. CrossRefGoogle Scholar
  13. Jaque D, Martínez Maestro L, del Rosal B, Haro-Gonzalez P, Benayas A, Plaza JL, Martín Rodríguez E, García Solé J (2014) Nanoparticles for photothermal therapies. Nanoscale 6:9494–9530. CrossRefGoogle Scholar
  14. Karakoti AS, Das S, Thevuthasan S, Seal S (2011) PEGylated inorganic nanoparticles. Angew Chem Int Ed 50:1980–1994. CrossRefGoogle Scholar
  15. Kim MH, Lu X, Wiley B, Lee EP, Xia Y (2008) Morphological evolution of single-crystal Ag nanospheres during the galvanic replacement reaction with HAuCl4. J Phys Chem C 112:7872–7876. CrossRefGoogle Scholar
  16. Kroll A, Pillukat MH, Hahn D, Schnekenburger J (2012) Interference of engineered nanoparticles with in vitro toxicity assays. Arch Toxicol 86:1123–1136. CrossRefGoogle Scholar
  17. Kumar R, Maitra AN, Patanjali PK, Sharma P (2005) Hollow gold nanoparticles encapsulating horseradish peroxidase. Biomaterials 26:6743–6753. CrossRefGoogle Scholar
  18. Langille MR, Personick ML, Zhang J, Mirkin CA (2011) Bottom-up synthesis of gold octahedra with tailorable hollow features. J Am Chem Soc 133:10414–10417. CrossRefGoogle Scholar
  19. Li Z, Xue-Feng Y, Xiao-Feng F, Zhong-Hua H, Kai-Yang L (2008) Surface plasmon resonance and field enhancement of Au/Ag alloyed hollow nanoshells. Chin Phys Lett 25:1776–1779. CrossRefGoogle Scholar
  20. Liang H, Wan L, Bai C, Jiang L (2005) Gold hollow nanospheres: tunable surface plasmon resonance controlled by interior-cavity sizes. J Phys Chem B 109:7795–7800. CrossRefGoogle Scholar
  21. Lindley SA, Cooper JK, Rojas-Andrade MD, Fung V, Leahy CJ, Chen S, Zhang JZ (2017) Highly tunable hollow gold nanospheres: gaining size control and uniform galvanic exchange of sacrificial cobalt boride scaffolds. ACS Appl Mater Interfaces 10:12992–13001. CrossRefGoogle Scholar
  22. Loo C, Lin A, Hirsch L, Lee M, Barton J, Halas N, West J, Drezek R (2004) Nanoshell-enabled photonics-based imaging and therapy of cancer. Technol Cancer Res Treat 3:33–40CrossRefGoogle Scholar
  23. Lu X, Chen J, Skrabalak SE, Xia Y (2008) Galvanic replacement reaction: a simple and powerful route to hollow and porous metal nanostructures. Proc Inst Mech Eng Part N J Nanoeng Nanosyst 221:1–16. CrossRefGoogle Scholar
  24. Lu W, Xiong C, Zhang G, Huang Q, Zhang R, Zhang JZ, Li C (2009) Targeted photothermal ablation of murine melanomas with melanocyte-stimulating hormone analog - conjugated hollow gold nanospheres. Clin Cancer Res 15:876–886. CrossRefGoogle Scholar
  25. Lu W, Huang Q, Ku G, Wen X, Zhou M, Guzatov D, Brecht P, Su R, Oraevsky A, Wang LV, Li C (2010) Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres. Biomaterials 31:2617–2626. CrossRefGoogle Scholar
  26. Lux F, Lerouge F, Bosson J, Lemercier G, Andraud C, Vitrant G, Baldeck PL, Chassagneux F, Parola S (2009) Gold hollow spheres obtained using an innovative emulsion process: towards multifunctional Au nanoshells. Nanotechnology 20:355603. CrossRefGoogle Scholar
  27. Melancon MP, Lu W, Yang Z, Zhang R, Cheng Z, Elliot AM, Stafford J, Olson T, Zhang JZ, Li C (2008) In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy. Mol Cancer Ther 7:1730–1739. CrossRefGoogle Scholar
  28. Melancon MP, Zhou M, Li C (2011) Cancer theranostics with near-infrared light-activatable multimodal nanoparticles. Acc Chem Res 44:947–956. CrossRefGoogle Scholar
  29. O’Neal DP, Hirsch LR, Halas NJ et al (2004) Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett 209:171–176. CrossRefGoogle Scholar
  30. Olson TY, Schwartzberg AM, Orme CA, Talley CE, O'Connell B, Zhang JZ (2008) Hollow gold-silver double-shell nanospheres: structure, optical absorption, and surface-enhanced raman scattering. J Phys Chem C 112:6319–6329. CrossRefGoogle Scholar
  31. Peña-Rodríguez O, González Pérez PP, Pal U (2011) MieLab: a software tool to perform calculations on the scattering of electromagnetic waves by multilayered spheres. Int J Spectrosc 2011:1–10. CrossRefGoogle Scholar
  32. Pfaller T, Colognato R, Nelissen I, Favilli F, Casals E, Ooms D, Leppens H, Ponti J, Stritzinger R, Puntes V, Boraschi D, Duschl A, Oostingh GJ (2010) The suitability of different cellular in vitro immunotoxicity and genotoxicity methods for the analysis of nanoparticle-induced events. Nanotoxicology 4:52–72. CrossRefGoogle Scholar
  33. Poudel BK, Gupta B, Ramasamy T, Thapa RK, Pathak S, Oh KT, Jeong JH, Choi HG, Yong CS, Kim JO (2017) PEGylated thermosensitive lipid-coated hollow gold nanoshells for effective combinational chemo-photothermal therapy of pancreatic cancer. Colloids Surf B 160:73–83. CrossRefGoogle Scholar
  34. Preciado-Flores S, Wang D, Wheeler DA, Newhouse R, Hensel JK, Schwartzberg A, Wang L, Zhu J, Barboza-Flores M, Zhang JZ (2011) Highly reproducible synthesis of hollow gold nanospheres with near infrared surface plasmon absorption using PVP as stabilizing agent. J Mater Chem 21:2344–2350. CrossRefGoogle Scholar
  35. Qin Y, Ji X, Jing J, Liu H, Wu H, Yang W (2010) Size control over spherical silver nanoparticles by ascorbic acid reduction. Colloids Surf A Physicochem Eng Asp 372:172–176. CrossRefGoogle Scholar
  36. Schwartzberg AM, Olson TY, Talley CE, Zhang JZ (2006) Synthesis, characterization, and tunable optical properties of hollow gold nanospheres. J Phys Chem B 110:19935–19944. CrossRefGoogle Scholar
  37. Shahjamali MM, Bosman M, Cao S, Huang X, Saadat S, Martinsson E, Aili D, Tay YY, Liedberg B, Loo SCJ, Zhang H, Boey F, Xue C (2012) Gold coating of silver nanoprisms. Adv Funct Mater 22:849–854. CrossRefGoogle Scholar
  38. Skrabalak SE, Chen J, Sun Y, Lu X, Au L, Cobley CM, Xia Y (2008) Gold nanocages: synthesis, properties and applications. Acc Chem Res 41:1587–1595. CrossRefGoogle Scholar
  39. Sun Y, Xia Y (2002) Increased sensitivity of surface plasmon resonance of gold nanoshells compared to that of gold solid colloids in response to environmental changes. Anal Chem 74:5297–5305. CrossRefGoogle Scholar
  40. Sun Y, Mayers BT, Xia Y (2002) Template-engaged replacement reaction: a one-step approach to the large-scale synthesis of metal nanostructures with hollow interiors. Nano Lett 2:481–485. CrossRefGoogle Scholar
  41. Sun Y, Mayers B, Xia Y (2003) Metal nanostructures with hollow interiors. Adv Mater 15:641–646. CrossRefGoogle Scholar
  42. Villa A, Snyder EY, Vescovi A, Martı́nez-Serrano A (2000) Establishment and properties of a growth factor-dependent, perpetual neural stem cell line from the human CNS. Exp Neurol 161:67–84. CrossRefGoogle Scholar
  43. Villa A, Navarro-Galve B, Bueno C, Franco S, Blasco ḾA, Martinez-Serrano A (2004) Long-term molecular and cellular stability of human neural stem cell lines. Exp Cell Res 294:559–570. CrossRefGoogle Scholar
  44. Vongsavat V, Vittur BM, Bryan WW, Kim JH, Lee TR (2011) Ultrasmall hollow gold-silver nanoshells with extinctions strongly red-shifted to the near-infrared. ACS Appl Mater Interfaces 3:3616–3624. CrossRefGoogle Scholar
  45. Wu G, Mikhailovsky A, Khant HA, Fu C, Chiu W, Zasadzinski JA (2008) Remotely triggered liposomal release by near-infrared light absorption via hollow gold nanoshells. J Am Chem Soc 130:8175–8177. CrossRefGoogle Scholar
  46. Xia Y, Campbell DJ (2007) Plasmons: why should we care? J Chem Educ 84:91. CrossRefGoogle Scholar
  47. You J, Zhang G, Li C (2010) Exceptionally high payload of doxorubicin in hollow gold nanospheres for mear-infrared light-triggered drug release. ACS Nano 4:1033–1041. CrossRefGoogle Scholar
  48. Yu M, Guo F, Wang J, Tan F, Li N (2016) A pH-driven and photoresponsive nanocarrier: remotely-controlled by near-infrared light for stepwise antitumor treatment. Biomaterials 79:25–35. CrossRefGoogle Scholar
  49. Zhang JZ (2010) Biomedical applications of shape-controlled plasmonic nanostructures: a case study of hollow gold nanospheres for photothermal ablation therapy of cancer. J Phys Chem Lett 1:686–695. CrossRefGoogle Scholar
  50. Zhang Q, Xie J, Yu Y, Lee JY (2010) Monodispersity control in the synthesis of monometallic and bimetallic quasi-spherical gold and silver nanoparticles. Nanoscale 2:1962–1975. CrossRefGoogle Scholar
  51. Zhang K, Holloway T, Wingfield A, Pradhan J, Cao W, K. Pradhan A (2011) Hollow gold nanospheres: growth, morphology, composition and absorption characteristics. Micro Nanosyst 3:76–82. CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Sayma Adriana Rodriguez-Montelongo
    • 1
  • Jesus Gonzalez-Hernandez
    • 2
  • Abel Hurtado Macias
    • 3
  • Ana Sonia Silva-Ramirez
    • 4
  • Claudia G. Castillo Martin del Campo
    • 5
  • Jose Manuel Gutierrez-Hernandez
    • 6
  • Facundo Ruiz
    • 1
  • Omar Gonzalez-Ortega
    • 4
    Email author
  1. 1.Facultad de CienciasUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  2. 2.Centro de Ingenieria y Desarrollo IndustrialQueretaroMexico
  3. 3.Centro de Investigacion en Materiales AvanzadosChihuahuaMexico
  4. 4.Facultad de Ciencias QuimicasUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  5. 5.Facultad de MedicinaUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico
  6. 6.Coordinacion para la Inovacion y la Aplicacion de la Ciencia y la TecnologiaUniversidad Autonoma de San Luis PotosiSan Luis PotosiMexico

Personalised recommendations