Journal of Materials Science

, Volume 54, Issue 6, pp 4997–5007 | Cite as

Biological effects of gold nanoclusters are evaluated by using silkworm as a model animal

  • Lin Ma
  • Vivian Andoh
  • Haiyan Liu
  • Jiangchao Song
  • Guohua WuEmail author
  • Long LiEmail author
Materials for life sciences


In this paper, Bombyx mori silkworm was used as a model animal to evaluate the biological effects of BSA-stabilized gold nanoclusters (BSA-Au NCs) via characterizing the growth status and silk properties of silkworms; the uptake of BSA-Au NCs by silkworms was realized by intravascular injection (the most dose of Au is 9.38 μg/silkworm). The results show that BSA-Au NCs have no obvious negative effects on the growth status of silkworms. WAXS and infrared results demonstrate that the crystalline or secondary structures of BSA-Au NCs-silks are not changed, but there is a slight increase in the helix/random coil content and a little decrease in the size and content of β-sheet compared with control-silks, suggesting that BSA-Au NCs confine the conformational transformation of silk fibroin to β-sheet from helix/random coil. Thermogravimetric analysis and tensile test results show that the thermal stability and mechanical properties (elongation at break, breaking strength and toughness modulus) of the BSA-Au NCs-silks are not weakened and the toughness modulus of the BSA-Au NCs-silks is increased, which may be attributed to the increase in the helix/random coil content. ICP-MS results demonstrate the accumulation and biodistribution of Au element in midgut, fat body and silk gland after the injection of 120 h, indicating that Au mainly distributes in midgut. In summary, BSA-Au NCs show no significant negative effect on silkworm when the dose of Au is below 9.38 μg/silkworm (about 6.25 mg kg−1). This study provides an efficient method for evaluating the biological effects of NCs, which will have a potential use in the biochemical field.



Thanks for the financial support from Earmarked Fund for Modern Agro-industry Technology Research System and Young Elite Scientist Sponsorship Program by CAST (2015QNRC001).

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest to declare.

Supplementary material

10853_2018_3213_MOESM1_ESM.docx (2.5 mb)
Supplementary material 1 (DOCX 2589 kb)


  1. 1.
    Kang S, Lee J, Ryu S et al (2017) Gold nanoparticle/graphene oxide hybrid sheets attached on mesenchymal stem cells for effective photothermal cancer therapy. Chem Mater 29(8):3461–3476Google Scholar
  2. 2.
    Liu JY, Peng Q (2017) Protein-gold nanoparticle interactions and their possible impact on biomedical applications. Acta Biomater 55:13–27Google Scholar
  3. 3.
    Hossain MZ, Maragos CM (2018) Gold nanoparticle-enhanced multiplexed imaging surface plasmon resonance (iSPR) detection of Fusarium mycotoxins in wheat. Biosens Bioelectron 101:245–252Google Scholar
  4. 4.
    Choudhary M, Brink R, Nandi D et al (2017) Gold nanoparticle within the polymer chain, a multifunctional composite material, for the electrochemical detection of dopamine and the hydrogen atom-mediated reduction of Rhodamine-B, a mechanistic approach. J Mater Sci 52(2):770–781. Google Scholar
  5. 5.
    Zhang XD, Chen J, Luo ZT et al (2014) Enhanced tumor accumulation of sub-2 nm gold nanoclusters for cancer radiation therapy. Adv Healthc Mater 3(1):133–141Google Scholar
  6. 6.
    Zhou FY, Feng B, Yu HJ et al (2016) Cisplatin prodrug-conjugated gold nanocluster for fluorescence imaging and targeted therapy of the breast cancer. Theranostics 6(5):679–687Google Scholar
  7. 7.
    Zhang XD, Luo ZT, Chen J et al (2014) Ultrasmall Au10–12(SG)10–12 nanomolecules for high tumor specificity and cancer radiotherapy. Adv Mater 26(26):4565–4568Google Scholar
  8. 8.
    Zhang XD, Wu D, Shen X et al (2012) In vivo renal clearance, biodistribution, toxicity of gold nanoclusters. Biomaterials 33(18):4628–4638Google Scholar
  9. 9.
    Dong LY, Li ML, Zhang S et al (2015) Cytotoxicity of BSA-stabilized gold nanoclusters: in vitro and in vivo study. Small 11(21):2571–2581Google Scholar
  10. 10.
    Chen HY, Li SL, Li BW et al (2012) Folate-modified gold nanoclusters as near-infrared fluorescent probes for tumor imaging and therapy. Nanoscale 4(19):6050–6064Google Scholar
  11. 11.
    Chen HY, Li BW, Ren XY et al (2012) Multifunctional near-infrared-emitting nano-conjugates based on gold clusters for tumor imaging and therapy. Biomaterials 33(33):8461–8476Google Scholar
  12. 12.
    Hamamoto H, Tonoike A, Narushima K et al (2009) Silkworm as a model animal to evaluate drug candidate toxicity and metabolism. Comp Biochem Phys C 149(3):334–339Google Scholar
  13. 13.
    Matsumot Y, Miyazaki S, Fukunag DH et al (2011) Quantitative evaluation of cryptococcal pathogenesis and antifungal drugs using a silkworm infection model with cryptococcus neoformans. J Appl Microbiol 112(1):138–146Google Scholar
  14. 14.
    Shi ZZ, Zhuang DH, Ilyin EA (1998) Space flight experiment on Chinese silkworm on board the Russian 10th Biosatellite. Adv Space Res 21(8–9):1145–1150Google Scholar
  15. 15.
    Liu T, Xing R, Zhou YF et al (2014) Hematopoiesis toxicity induced by CdTe quantum dots determined in an invertebrate model organism. Biomaterials 35(9):2942–2951Google Scholar
  16. 16.
    Xing R, Li KL, Zhou YF et al (2016) Impact of fluorescent silicon nanoparticles on circulating hemolymph and hematopoiesis in an invertebrate model organism. Chemosphere 159:628–637Google Scholar
  17. 17.
    Toshiki T, Chantal T, Corinne R et al (2000) Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector. Nat Biotechnol 18(1):81–84Google Scholar
  18. 18.
    Otsuki R, Yamamoto M, Matsumoto E et al (2017) Bioengineered silkworms with butterfly cytotoxin-modified silk glands produce sericin cocoons with a utility for a new biomaterial. Proc Natl Acad Sci USA 114(26):6740–6745Google Scholar
  19. 19.
    Qin J, He NJ, Xiang ZH (2010) Advances in silkworm modeling research. Sci Seric 36(4):0645–0649Google Scholar
  20. 20.
    Kaito C, Akimitsu N, Watanabe H et al (2002) Silkworm larvae as an animal model of bacterial infection pathogenic to humans. Microb Pathog 32(4):183–190Google Scholar
  21. 21.
    Hamamoto H, Kurokawa K, Kaito C et al (2004) Quantitative evaluation of the therapeutic effects of antibiotics using silkworms infected with human pathogenic microorganisms. Antimicrob Agents Chemother 48(3):774–779Google Scholar
  22. 22.
    Panthee S, Paudel A, Hamamoto H et al (2017) Advantages of the silkworm as an animal model for developing novel antimicrobial agents. Front Microbiol. Google Scholar
  23. 23.
    Xie JP, Zheng YG, Ying JY (2009) Protein-directed synthesis of highly fluorescent gold nanoclusters. J Am Chem Soc 131(3):888–889Google Scholar
  24. 24.
    Ma L, Akurugu MA, Andoh V et al (2018) Intrinsically reinforced silks obtained by incorporation of graphene quantum dots into silkworms. Sci China Mater. Google Scholar
  25. 25.
    Cai LY, Shao HL, Hu XC et al (2015) Reinforced and ultraviolet resistant silks from silkworms fed with titanium dioxide nanoparticles. ACS Sustain Chem Eng 3(10):2551–2557Google Scholar
  26. 26.
    Cheng L, Huang HM, Chen SY et al (2017) Characterization of silkworm larvae growth and properties of silk fibres after direct feeding of copper or silver nanoparticles. Mater Des 129:125–134Google Scholar
  27. 27.
    Wu GH, Song P, Zhang DY et al (2017) Robust composite silk fibers pulled out of silkworms directly fed with nanoparticles. Int J Biol Macromol 104(Pt A):533–538Google Scholar
  28. 28.
    Shao JZ, Zheng JH, Liu JQ et al (2005) Fourier transform Raman and fourier transform infrared spectroscopy studies of silk fibroin. J Appl Polym Sci 96(6):1999–2004Google Scholar
  29. 29.
    Ling SJ, Qi ZM, Knight DP et al (2011) Synchrotron FTIR microspectroscopy of single natural silk fibers. Biomacromolecules 12(9):3344–3349Google Scholar
  30. 30.
    Das S, Pati D, Tiwari D et al (2012) Synthesis of silk fibroin–glycopolypeptide conjugates and their recognition with lectin. Biomacromolecules 13(11):3695–3702Google Scholar
  31. 31.
    Lu Q, Hu X, Wang XQ et al (2010) Water-insoluble silk films with silk I structure. Acta Biomater 6(4):1380–1387Google Scholar
  32. 32.
    Zhou SB, Peng HS, Yu XJ et al (2008) Preparation and characterization of a novel electrospun spider silk fibroin/poly(d,l-lactide) composite fiber. J Phys Chem B 112(36):11209–11216Google Scholar
  33. 33.
    Chen X, Shao ZZ, Marinkovic NS et al (2001) Conformation transition kinetics of regenerated Bombyx mori silk fibroin membrane monitored by time-resolved FTIR spectroscopy. Biophys Chem 89(1):25–34Google Scholar
  34. 34.
    Lin NB, Cao LW, Huang QL et al (2016) Functionalization of silk fibroin materials at mesoscale. Adv Funct Mater 26(48):8885–8902Google Scholar
  35. 35.
    He YX, Zhang NN, Li WF et al (2012) N-terminal domain of Bombyx mori fibroin mediates the assembly of silk in response to pH decrease. J Mol Biol 418(3–4):197–207Google Scholar
  36. 36.
    Zhang HC, Bhunia K, Munoz N et al (2017) Linking morphology changes to barrier properties of polymeric packaging for microwave-assisted thermal sterilized food. J Appl Polym Sci 134:45481Google Scholar
  37. 37.
    Yen FS, Chen WC, Yang JM et al (2002) Crystallite size variations of nanosized Fe2O3 powders during γ- to α-phase transformation. Nano Lett 2(3):245–252Google Scholar
  38. 38.
    Sampath S, Isdebski T, Jenkins JE et al (2012) X-ray diffraction study of nanocrystalline and amorphous structure within major and minor ampullate dragline spider silks. Soft Matter 8(25):6713–6722Google Scholar
  39. 39.
    Numata K, Sato R, Yazawa K et al (2015) Crystal structure and physical properties of Antheraea yamamai silk fibers: long poly(alanine) sequences are partially in the crystalline region. Polymer 77:87–94Google Scholar
  40. 40.
    Grubb DT, Ji G (1999) Molecular chain orientation in supercontracted and re-extended spider silk. Int J Biol Macromol 24(2–3):203–210Google Scholar
  41. 41.
    Du N, Liu XY, Narayanan J et al (2006) Design of superior spider silk: from nanostructure to mechanical properties. Biophys J 91(12):4528–4535Google Scholar
  42. 42.
    Wang Q, Wang CY, Zhang MC et al (2016) Feeding single-walled carbon nanotubes or graphene to silkworms for reinforced silk fibers. Nano Lett 16(10):6695–6700Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of BiotechnologyJiangsu University of Science and TechnologyZhenjiangPeople’s Republic of China
  2. 2.The Sericultural Research InstituteChinese Academy of Agricultural SciencesZhenjiangPeople’s Republic of China
  3. 3.Laboratory of Risk Assessment for Sericultural Products and Edible InsectsMinistry of AgricultureZhenjiangPeople’s Republic of China
  4. 4.Department of Tea and Food TechnologyJiangsu Vocational College of Agriculture and ForestryJurongPeople’s Republic of China

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