Analytical and Bioanalytical Chemistry

, Volume 401, Issue 3, pp 809–816

Imaging the cellular uptake of tiopronin-modified gold nanoparticles


  • Xiaoqing Cai
    • Institute of PhysicsAcademia Sinica
  • Hsiang-Hsin Chen
    • Institute of PhysicsAcademia Sinica
  • Cheng-Liang Wang
    • Institute of PhysicsAcademia Sinica
  • Shin-Tai Chen
    • Institute of PhysicsAcademia Sinica
  • Sheng-Feng Lai
    • Institute of PhysicsAcademia Sinica
  • Chia-Chi Chien
    • Institute of PhysicsAcademia Sinica
    • Department of Engineering and System ScienceNational Tsing Hua University
  • Yi-Yun Chen
    • Institute of PhysicsAcademia Sinica
  • Ivan M. Kempson
    • Institute of PhysicsAcademia Sinica
    • Institute of PhysicsAcademia Sinica
    • Department of Engineering and System ScienceNational Tsing Hua University
    • Institute of Optoelectronic SciencesNational Taiwan Ocean University
  • C. S. Yang
    • Center for NanomedicineNational Health Research Institutes
  • G. Margaritondo
    • Ecole Polytechnique Fédérale de Lausanne (EPFL)
Original Paper

DOI: 10.1007/s00216-011-4986-3

Cite this article as:
Cai, X., Chen, H., Wang, C. et al. Anal Bioanal Chem (2011) 401: 809. doi:10.1007/s00216-011-4986-3


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 nanoparticlesX-ray synthesisCellular uptakeTransmission X-ray microscopy

Supplementary material

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

Copyright information

© Springer-Verlag 2011