Invited Speaker Australian & New Zealand Society of Magnetic Resonance Conference 2017

Nanoassemblies of paramagnetic amphiphilic chelates as advanced MRI contrast agents (#72)

Abhishek Gupta 1
  1. Nanoscale Organisation and Dynamics Group, School of Science and Health, Western Sydney University, Penrith

Paramagnetic contrast agents (CAs) are routinely used in magnetic resonance imaging (MRI) to enhance image contrast between diseased and normal tissue.[1] However, as most of the present commercially available CAs have moderate relaxivity (efficiency) and restricted specificity and targeting ability, large doses (~500 mM Gd (III)) are often administered to obtain sufficient contrast. This in turn exacerbates the potentially toxic nature of these agents, especially in patients with weak renal function.[2] Therefore, stable target specific CAs with high relaxivity (efficiency) are desired in MRI to get better contrast at low doses. Supramolecular self-assembled nanoparticles, hereafter referred to as nanoassemblies, made of paramagnetic amphiphilic chelates, exhibit many properties deemed important for an ideal MRI CA. These include improved relaxivity due to their slow molecular reorientation, their ability to deliver high payloads of paramagnetic metal ions, ease of altering their sizes by extruding them through polycarbonate filters, their ability to passively target tumours through enhanced permeation and retention, and their ability to incorporate (active) targeting moieties or therapeutic drugs within their framework to form combined therapeutic and diagnostic (theranostic) nanomedicines.[3-4This presentation reports on the design, synthesis, characterisation and relaxation properties of the highly ordered supramolecular nanoassemblies of novel paramagnetic amphiphilic chelates as advanced MRI CAs.[5-9] In addition, the development and characterisation of hypoxia (oxygen deprived tumorous tissue)-specific paramagnetic nanoassemblies is also presented. The rationally designed and synthesised paramagnetic amphiphiles were dispersed in an aqueous solution either by themselves or after mixing them with (commercial) phospholipids and/or amphiphilic targeting moieties. The shape and size of the nanostructures were comprehensively characterised. Their molecular parameters, such as reorientational correlation time and water exchange rate, were determined from the analysis of variable field 1H longitudinal relaxation rate measurements (also termed as the NMRD profiles) obtained on a fast field cycling relaxometer.

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  2. [4] K. Nicolay, G. J. Strijkers, H. Grull. in The chemistry of contrast agents in medical magnetic resonance imaging (Eds. Merbach AE, Helm L, Tóth É) 2013, pp. 449-487 (Wiley: Chichester). [5] A. Gupta, L. de Campo, B. Rehmanjan, S. A. Willis, L. J. Waddington, T. Stait-Gardner, et al., Langmuir. 2015, 31, 1556. [6] A. Gupta, L. de Campo, L. J. Waddington, R. B. Knott, D. Hwang, N. Kirby, et al., New J Chem. 2017, 41, 2735.
  3. [7] A. Gupta, T. Stait-Gardner, L. de Campo, L. J. Waddington, N. Kirby, W. S. Price, et al., J Mater Chem B. 2014, 2, 1225. [8] A. Gupta, S. A. Willis, T. Stait-Gardner, M. J. Moghaddam, W. S. Price, Magn Reson Chem. 2016, 54, 58. [9] A. Gupta, S. A. Willis, L. J. Waddington, T. Stait-Gardner, L. de Campo, D. W. Hwang, et al., Chem Eur J. 2015, 21, 13950.