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.

中文翻译：

---

阳离子mPEG刷嵌段共聚物与聚poly钨酸[[Gd（W ₅ O ₁₈）₂ ] ^9−的纳米组装形成稳定的高弛豫性MRI造影剂†

掺入顺磁性离子（例如g）的多金属氧酸盐（POM）有望作为造影剂用于磁共振成像（MRI）。具体而言，[Gd（W ₅ O ₁₈）₂ ] ^9-据报道（以GdWO为代表）比市售的造影剂具有更高的松弛度，但其临床应用受到POM在生理pH值（7.4）内在不稳定性的限制。在本报告中，我们对pH范围为5.0-7.4的纯GdWO和嵌段共聚物与GdWO的纳米组装进行稳定性研究，以评估其作为MRI造影剂的适用性。干净的GdWO仅在pH 5.4和6.4之间保持结构稳定性，并且在pH 7.4时显示出差的MRI对比度。为了解决此pH值的不稳定性，将GdWO与含有20或40个衍生自阳离子单体甲基丙烯酸2-二甲基氨基乙酯（DMAEMA）的单元的阳离子mPEG刷嵌段共聚物进行自组装。合成了具有不同电荷比的纳米组件，并根据其尺寸，稳定性，对比鲜明的特性和毒性。纵向松弛度（发现纳米组件的r ₁）取决于电荷比，而不取决于阳离子聚合物嵌段的长度。对PDMAEMA ₂₀纳米组件的进一步研究表明，它们在5.0至7.4的pH范围内是稳定的，与纯GdWO（2.77 s ^-1 mM ^-1）或临床MRI造影剂Gd-DTPA（4.1 s）相比，具有更高的r ₁。pH 7.4时为^-1 mM ^-1）。重要的是，具有最低荷电比（0.2）的纳米组件显示出最高的r ₁（12.1 s ^-1 mM ^-1），同时在研究的pH范围内稳定GdWO，对MDA-MB231细胞产生低毒性。