Physiological microenvironment-responsive contrast agent for magnetic resonance imaging

我们已经探索了智能MRI造影剂，可以描述正常和肿瘤组织之间病理生理状态的微环境差异。Gd离子组成的MRI造影剂可以缩短周围水分子中质子的T1弛豫时间，增强MRI信号。因此，人们可以通过调节Gd离子的水化行为来改变其信号增强活性。为了调节Gd离子在pH变化下的水化行为，我们重点研究了由一对弱酸性和弱碱性聚合物组成的多离子复合物（PIC）。这些带相反电荷的多离子在其静电等效电荷比下稳定地形成PIC，并伴随着水分子的释放。这种络合物的形成和水合行为受到pH值的显著影响，因为pH值的变化破坏了络合物中的电荷平衡。在之前的研究中，我们已经证明了PIC中负载的Gd离子的t1松弛活性受到pH的显著影响，并且在中性pH下受到抑制。我们进一步扩展了研究，以估计PIC为基础的药物在肿瘤成像中的潜力。我们改进了基于pic的药物的聚合物结构，以彻底抑制药物在中性ph下的t1 -松弛活性。然后对结肠癌小鼠进行了体内MRI成像研究。

We have explored intelligent MRI contrast agents which depict microenvironmental differences in pathophysiological states between normal and tumor tissues. MRI contrast agents consisting of Gd ion shorten the T1 -relaxation time of protons in surrounding water molecules to enhance MRI signals. Thus, one can modify the signal enhancement activity of Gd ions by regulating its hydration behavior. In order to regulate hydration behavior of Gd ions in response to pH changes, we have focused on a polyion complex (PIC) composed of a couple of weakly acidic and basic polymers. The stable PIC formation between these oppositely charged polyions at their electrostatically equivalent charge ratio accompanies with the release of water molecules. This complex formation and hydration behavior are significantly affected by pH, since pH change disorders the charge balance in the complex. In previous study, we had demonstrated that T1-relaxation activity of Gd ions loaded in the PIC considerably influenced by pH and suppressed at neutral pH. We further extended the study to estimate potentiality of the PIC-based agent in tumor imaging. We refined the polymer structure of PIC-based agent to thoroughly suppress T1-relaxation activity of the agent at neutral pH. Then, in vivo MRI imaging study with mice bearing colon 26 carcinoma were studied.