Herein, two water‐soluble PROXYL‐based magnetic resonance imaging (MRI) macromolecular organic contrast agents (mORCAs) are designed and synthesized: linear and cross‐linked PCE‐mPEG‐Ppa‐PROXYL. They are prepared by conjugating linear and cross‐linked poly(carboxylate ester) (PCE) with poly(ethylene glycol) (mPEG₂₀₀₀)‐modified nitroxides (PROXYL), respectively. Both mORCAs form self‐assembled aggregates in an aqueous phase and PROXYL is protected inside a hydrophobic core to achieve great resistance to reduction in the physiological environment, and they have low toxicity. Since cross‐linked PCE‐mPEG‐Ppa‐PROXYL possess a branched architecture, its self‐assembled aggregate is more stable and compact with a greater particle size. Cross‐linked PCE‐mPEG‐Ppa‐PROXYL outperform the linear one in the following aspects: 1) its longitudinal relaxivity (r ₁ = 0.79 mm ⁻¹ s⁻¹) is higher than that of the linear one (r ₁ = 0.64 mm ⁻¹ s⁻¹) and both excel the best mORCA reported so far (r ₁ = 0.42 mm ⁻¹ s⁻¹); 2) its blood retention time (≈48 h) is longer than that of its linear counterpart (≈10 h); 3) cross‐linked PCE‐mPEG‐Ppa‐PROXYL provided better MR imaging contrast resolution in normal organs (liver and kidney) and tumor of mice than the linear one. Overall, cross‐linked PCE‐mPEG‐Ppa‐PROXYL may have great potential to be a novel metal‐free macromolecular contrast agent for MR imaging.

中文翻译：

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通过将氮氧化物与聚乙二醇化的交联聚（羧酸酯）共轭来增强无金属MRI造影剂的功效。

本文设计并合成了两种水溶性的基于PROXYL的磁共振成像（MRI）高分子有机造影剂（mORCA）：线性和交联的PCE-mPEG-Ppa-PROXYL。它们是通过将线性和交联的聚（羧酸酯）（PCE）与聚（乙二醇）（mPEG ₂₀₀₀）-改性氮氧化物（PROXYL）。两种mORCAs均在水相中形成自组装聚集体，PROXYL在疏水核内部得到保护，从而对生理环境的还原具有很大的抵抗力，并且毒性低。由于交联的PCE-mPEG-Ppa-PROXYL具有分支结构，因此其自组装聚集体更稳定，更紧凑，并且粒径更大。交联的PCE-mPEG-Ppa-PROXYL在以下方面优于线性的：1）其纵向弛豫性（r ₁  = 0.79 m m ^-1 s ^-1）高于线性的（r ₁  = 0.64 m m ^-1 s ^-1）和两者均优于迄今为止报告的最佳mORCA（r ₁  = 0.42 m m ^-1 s ^-1）；2）它的血液保留时间（≈48小时）比其线性对应物的血液保留时间（≈10小时）更长；3）交联的PCE-mPEG-Ppa-PROXYL在小鼠的正常器官（肝和肾）和肿瘤中提供的MR成像对比分辨率要好于线性成像。总体而言，交联的PCE-mPEG-Ppa-PROXYL可能具有成为MR成像的新型无金属大分子造影剂的巨大潜力。