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Design, synthesis, physical and chemical characterisation, and biological interactions of lectin-targeted latex nanoparticles bearing Gd–DTPA chelates: an exploration of magnetic resonance molecular imaging (MRMI)

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Abstract

The physical and chemical parameters involved in the design and synthesis of biospecifically targeted nanoparticulate contrast media for magnetic resonance molecular imaging (MRMI) were explored in this pilot investigation. Latex nanoparticles 100, 400 and 900 nm in diameter were doubly derivatised, first with tomato lectin and then with gadoliniumIII-diethylenetriamine pentaacetic acid (Gd-chelates) to target them to epithelial and endothelial glycocalyceal N-glycans and to generate contrast enhancement in magnetic resonance imaging (MRI). After intravenous injection into mice, human placental cotyledons or human Vena saphena magna, contrasty images of the vascular structures were obtained in 1.5 T MRI with spatial resolution 0.1 mm in the imaging plane and 0.6 mm in the z axis, persisting >60 min and resistant to washing out by buffer rinses. Ultrastructural analysis of the nanoparticles revealed the targeting groups at the nanoparticle surfaces and the distribution of the Gd-chelates within the nanoparticles and enabled counts for use in determining relaxivity. The relaxivity values revealed were extremely high, accounting for the strong MR signals observed. Occasionally, nanoparticles larger than 100 nm were seen in close spatial association with disrupted regions of cell membrane or of collagen fibrils in the extracellular matrix. The data suggest that 100-nm nanoparticles generate adequate contrast for MRMI and cause least disruption to endothelial cell surfaces.

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Acknowledgements

The Austrian National Bank supported all stages of this work through the Jubilee Fund, projects 9273 and 10844. The Medical Research Fund Tirol provided financial support to this work. The Faustus Forschung Translational Drug Development AG provided financial support to this work. The Austrian Nano-Initiative co-financed this work as part of the Nano-Health project (no. 0200), the sub-project NANO-MRI being financed by the Austrian FWF (Fonds zur Förderung der Wissenschaftlichen Forschung) (Project no. N210-NAN). Dr. A. Wilder and Dr. T. Hanitz (Analytical Systems GmbH, Oberhausen, Germany) provided significant logistical support and insights concerning photon correlation spectroscopy. We thank Silvia Fill, Angelika Flörl and Beate Schimpfössl for excellent technical assistance. Our analyses of the various types of images would not have been possible without the excellent supporting services provided by Dr. J. Stöckler and Dr. W. Morscher of the Central Informatics Service of the University of Innsbruck.

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Authors and Affiliations

  1. Institute of Inorganic Chemistry, University of Vienna, Währingerstrasse 42, 1090, Vienna, Austria

    Irena Paschkunova-Martic, Mathea Sophia Galanski & Bernhard Keppler

  2. Department of Radiology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    Christian Kremser

  3. Department of Histology and Molecular Cell Biology, Innsbruck Medical University, Müllerstrasse 59, 6020, Innsbruck, Austria

    Klaudia Mistlberger, Nadezhda Shcherbakova, Kristian Pfaller, Isabella Höliner & Paul Debbage

  4. Central Laboratory Animal Facilities, Innsbruck Medical University, Peter-Mayr-Straße 4A, 6020, Innsbruck, Austria

    Hermann Dietrich & Yiping Zou

  5. Department of Surgery, Division of Vascular Surgery, University Hospital Innsbruck, Innsbruck Medical University, Anichstraße 35, 6020, Innsbruck, Austria

    Beate Hugl

  6. Institute for Medical Chemistry and Biochemistry, Innsbruck Medical University, Fritz-Pregl-Straße 3, 6020, Innsbruck, Austria

    Heribert Talasz

  7. Department of Gynaecology and Obstetrics, University Hospital Innsbruck, Innsbruck Medical University, Anichstraße 35, 6020, Innsbruck, Austria

    Elisabeth Sölder

  8. Tirol Land Hospital, Anichstraße 35, 6020, Innsbruck, Austria

    Wolfgang Buchberger

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  1. Irena Paschkunova-Martic
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Correspondence to Paul Debbage.

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Paschkunova-Martic, I., Kremser, C., Mistlberger, K. et al. Design, synthesis, physical and chemical characterisation, and biological interactions of lectin-targeted latex nanoparticles bearing Gd–DTPA chelates: an exploration of magnetic resonance molecular imaging (MRMI). Histochem Cell Biol 123, 283–301 (2005). https://doi.org/10.1007/s00418-005-0780-7

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