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Issue 6, 2014
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Gadolinium-DTPA amphiphile nanoassemblies: agents for magnetic resonance imaging and neutron capture therapy

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Abstract

Engineering biocompatible and physiologically stable nanoscaled therapeutics and imaging agents with the ability to target tumor tissue is a key challenge for the advancement of cancer therapeutics and diagnostic imaging. Here, we present chelating amphiphiles with the capacity to form nanoassembled colloidal particles containing high payloads of gadolinium (Gd) ions. We present the in situ synthesis and complexation of Gd with colloidal nanoassemblies (NAs) based on diethylenetriamine pentaacetic acid (DTPA) amphiphiles. This method allows for facile simultaneous incorporation of several metal ions for applications in multimodal imaging and therapeutics. The diverse internally nanostructured NAs made from sole precursor amphiphiles and their Gd-complexes were investigated by synchrotron small angle X-ray scattering (SAXS) and cryo-TEM. Depending on the molecular structure of the amphiphiles, the structures of NAs range from micelles to liposomes, to colloidal particles of inverse hexagonal (hexosomes) and inverse bicontinuous cubic phases (cubosomes), to multilayered nanospheres. The in vitro contrast activity of these NAs exhibited high relaxivity values as T1-weighted magnetic resonance imaging (MRI) contrast enhancement agents. Further, an α-Flag antibody fragment (Fab′) was bioconjugated to the surface of the Gd-complexed NAs. The binding ability of these targeted NAs to a FLAG-tagged protein was confirmed by SDS-PAGE. The in vitro cytotoxicity against two cell lines showed that except for the negatively charged micellar Gd-DTPA amphiphile, liposomal and higher order internally nanostructured NAs had low cell toxicity. The efficient cellular uptake of Gd-NAs by melanoma cancer cells was also investigated.

Graphical abstract: Gadolinium-DTPA amphiphile nanoassemblies: agents for magnetic resonance imaging and neutron capture therapy

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Publication details

The article was received on 01 Oct 2013, accepted on 15 Jan 2014 and first published on 17 Feb 2014


Article type: Paper
DOI: 10.1039/C3BM60235D
Biomater. Sci., 2014,2, 924-935
  • Open access: Creative Commons BY license
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    Gadolinium-DTPA amphiphile nanoassemblies: agents for magnetic resonance imaging and neutron capture therapy

    M. J. Moghaddam, L. de Campo, M. Hirabayashi, P. A. Bean, L. J. Waddington, J. A. Scoble, G. Coia and C. J. Drummond, Biomater. Sci., 2014, 2, 924
    DOI: 10.1039/C3BM60235D

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