Nano-assemblies of cationic mPEG brush block copolymers with gadolinium polyoxotungstate [Gd(W ₅ O ₁₈ ) ₂ ] ⁹⁻ form stable, high relaxivity MRI contrast agents

Polyoxometalates (POMs) incorporating paramagnetic ions, such as gadolinium, show promise as contrast agents for application in magnetic resonance imaging (MRI). Specifically, [Gd(W5O18)2]9- (denoted as GdWO) has been reported to have a higher relaxivity than commercially available contrast agents, but it's clinical utility has been limited by the intrinsic instability of POMs at physiological pH (7.4). In the current report we present a stability study on neat GdWO and nano-assemblies of block copolymers with GdWO in the pH range 5.0-7.4 to assess their suitability as MRI contrast agents. Neat GdWO only maintained structural stability between pH 5.4 and 6.4, and demonstrated poor MRI contrast at pH 7.4. To address this pH instability, GdWO was self-assembled with cationic mPEG brush block copolymers containing 20 or 40 units derived from the cationic monomer, 2-dimethylaminoethyl methacrylate (DMAEMA). Nano-assemblies with different charge ratios were synthesised and characterised according to their size, stability, contrasting properties and toxicity. The longitudinal relaxivity (r1) of the nano-assemblies was found to be dependent on the charge ratio, but not on the length of the cationic polymer block. Further investigation of PDMAEMA20 nano-assemblies demonstrated that they were stable over the pH range 5.0-7.4, exhibiting a higher r1 than either neat GdWO (2.77 s-1 mM-1) or clinical MRI contrast agent Gd-DTPA (4.1 s-1 mM-1) at pH 7.4. Importantly, the nano-assembly with the lowest charge ratio (0.2), showed the highest r1 (12.1 s-1 mM-1) whilst, stabilising GdWO over the pH range studied, eliciting low toxicity with MDA-MB231 cells.