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Imaging and quantifying the morphology of an organic–inorganic nanoparticle at the sub-nanometre level

Abstract

The development of hybrid organic–inorganic nanoparticles is of interest for applications such as drug delivery, DNA and protein recognition, and medical diagnostics. However, the characterization of such nanoparticles remains a significant challenge due to the heterogeneous nature of these particles. Here, we report the direct visualization and quantification of the organic and inorganic components of a lipid-coated silica particle that contains a smaller semiconductor quantum dot. High-angle annular dark-field scanning transmission electron microscopy combined with electron energy loss spectroscopy was used to determine the thickness and chemical signature of molecular coating layers, the element atomic ratios, and the exact positions of different elements in single nanoparticles. Moreover, the lipid ratio and lipid phase segregation were also quantified.

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Figure 1: Overview of the intermediate steps involved in the synthesis of lipid-coated, QD-containing silica nanoparticles.
Figure 2: Spatially resolved element analysis of the hybrid QD@SiO2@lipids nanoparticles.
Figure 3: Effect of the electron beam on the lipid layer of the hybrid inorganic/organic QD@SiO2@lipids nanoparticles.
Figure 4: Visualization, quantification and molecular characterization of the different steps involved in the synthesis of QD@SiO2@lipid nanoparticles.
Figure 5: Full-field, relative quantification of the different elements in the hybrid lipid-coated QD@SiO2 nanoparticles and of the lipid ratio in the lipid layer.

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Acknowledgements

The authors would like to thank C. Morin, I. Swart, A. Juhin, E. de Smit and H. van Hattum for useful discussions. M. Kociak and M. Tencé are gratefully acknowledged for their help in designing the liquid-nitrogen STEM cooling stage. This work was financially supported by the I3 European project ESTEEM (no. 026019) and a VICI grant (F.M.F.d.G.) of the Netherlands Organization for Scientific Research (NWO-CW).

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Contributions

M.M.v.S. designed the experiment with help from F.M.F.d.G. M.M.v.S. synthesized the hybrid nanoparticles, processed the data and wrote the manuscript. A.G., O.S. and L.F.Z. performed the STEM-HAADF and EELS measurements, together with M.M.v.S. W.J.M.M., R.K., M.M.v.S. and A.M. played a major role in the design and development of the hybrid nanoparticles. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Matti M. van Schooneveld or Frank M. F. de Groot.

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The authors declare no competing financial interests.

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van Schooneveld, M., Gloter, A., Stephan, O. et al. Imaging and quantifying the morphology of an organic–inorganic nanoparticle at the sub-nanometre level. Nature Nanotech 5, 538–544 (2010). https://doi.org/10.1038/nnano.2010.105

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