Analytical and Bioanalytical Chemistry

, Volume 401, Issue 3, pp 809–816

Imaging the cellular uptake of tiopronin-modified gold nanoparticles

  • Xiaoqing Cai
  • Hsiang-Hsin Chen
  • Cheng-Liang Wang
  • Shin-Tai Chen
  • Sheng-Feng Lai
  • Chia-Chi Chien
  • Yi-Yun Chen
  • Ivan M. Kempson
  • Yeukuang Hwu
  • C. S. Yang
  • G. Margaritondo
Original Paper


Well-dispersed gold nanoparticles (NP) coated with tiopronin were synthesized by X-ray irradiation without reducing agents. High-resolution transmission electron microscopy shows that the average core diameters of the NPs can be systematically controlled by adjusting the tiopronin to Au mole ratio in the reaction. Three methods were used to study the NP uptake by cells: quantitative measurements by inductively coupled plasma mass spectrometry, direct imaging with high lateral resolution transmission electron microscopy and transmission X-ray microscopy. The results confirmed that the NP internalization mostly occurred via endocytosis and concerned the cytoplasm. The particles, in spite of their small sizes, were not found to arrive inside the cell nuclei. The synthesis without reducing agents and solvents increased the biocompatibility as required for potential applications in analysis and biomedicine in general.


A high resolution Transmission X-ray microscope image (A) captured the internalization and aggregation of tiopronin-coated Au nanoparticles in the vicinity of cell nucleus, the light dark area, of an EMG-6 cell. (B) One of the corresponding pictures produced by three-dimensional tomography reconstruction. The complete movie sequence of such pictures provides three-dimensional visual confirmation of the internalization and location of tiopronin-coated Au nanoparticles.


Gold nanoparticles X-ray synthesis Cellular uptake Transmission X-ray microscopy 

Supplementary material

216_2011_4986_MOESM1_ESM.mpg (7.6 mb)
ESM 1(MPG 7801 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Xiaoqing Cai
    • 1
  • Hsiang-Hsin Chen
    • 1
  • Cheng-Liang Wang
    • 1
  • Shin-Tai Chen
    • 1
  • Sheng-Feng Lai
    • 1
  • Chia-Chi Chien
    • 1
    • 2
  • Yi-Yun Chen
    • 1
  • Ivan M. Kempson
    • 1
  • Yeukuang Hwu
    • 1
    • 2
    • 3
  • C. S. Yang
    • 4
  • G. Margaritondo
    • 5
  1. 1.Institute of PhysicsAcademia SinicaTaipeiTaiwan
  2. 2.Department of Engineering and System ScienceNational Tsing Hua UniversityHsinchuTaiwan
  3. 3.Institute of Optoelectronic SciencesNational Taiwan Ocean UniversityKeelungTaiwan
  4. 4.Center for NanomedicineNational Health Research InstitutesMiaoliTaiwan
  5. 5.Ecole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland

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