Zhang Songbai, Lloveras Vega, Pulido Daniel, Liko Flonja, Pinto Luiz F, Albericio Fernando, Royo Miriam, Vidal-Gancedo José
Institut de Ciència de Materials de Barcelona (ICMAB-CSIC) and CIBER-BBN, Campus Universitari de Bellaterra, Bellaterra, 08193 Barcelona, Spain.
Institut de Química Avançada de Catalunya (IQAC-CSIC) and CIBER-BBN c/ Jordi Girona 18-26, 08034 Barcelona, Spain.
Pharmaceutics. 2020 Aug 14;12(8):772. doi: 10.3390/pharmaceutics12080772.
Finding alternatives to gadolinium (Gd)-based contrast agents (CA) with the same or even better paramagnetic properties is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of entirely organic metal-free paramagnetic macromolecules based on biocompatible oligoethylene glycol dendrimers fully functionalized with 5 and 20 organic radicals (OEG Gn-PROXYL ( = 0, 1) radical dendrimers) with the aim to be used as magnetic resonance imaging (MRI) contrast agents. Conferring high water solubility on such systems is often a concern, especially in large generation dendrimers. Our approach to overcome such an issue in this study is by synthesizing dendrimers with highly water-soluble branches themselves. In this work, we show that the highly water-soluble OEG Gn-PROXYL ( = 0, 1) radical dendrimers obtained showed properties that convert them in good candidates to be studied as contrast agents for MRI applications like diagnosis and follow-up of infectious diseases, among others. Importantly, with the first generation radical dendrimer, a similar relaxivity value (3.4 mMs) in comparison to gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) used in clinics (3.2 mMs, r.t. 7T) has been obtained, and it has been shown to not be cytotoxic, avoiding the toxicity risks associated with the unwanted accumulation of Gd in the body.
寻找具有相同甚至更好顺磁特性的钆（Gd）基造影剂（CA）替代品对于克服其已确定的毒性至关重要。在此，我们描述了基于生物相容性低聚乙二醇树枝状大分子的完全有机无金属顺磁大分子的合成与表征，该树枝状大分子用5个和20个有机自由基完全官能化（OEG Gn - PROXYL（= 0, 1）自由基树枝状大分子），旨在用作磁共振成像（MRI）造影剂。赋予此类体系高水溶性往往是一个问题，尤其是在大代树枝状大分子中。我们在本研究中克服这一问题的方法是合成本身具有高水溶性分支的树枝状大分子。在这项工作中，我们表明所获得的高水溶性OEG Gn - PROXYL（= 0, 1）自由基树枝状大分子具有一些特性，使其成为用于MRI应用（如传染病诊断和随访等）造影剂研究的良好候选物。重要的是，第一代自由基树枝状大分子与临床使用的钆 - 二乙烯三胺五乙酸（Gd - DTPA）相比，获得了相似的弛豫率值（3.4 mM s⁻¹）（临床使用的Gd - DTPA在室温7T下为3.2 mM s⁻¹），并且已证明它无细胞毒性，避免了与体内钆不必要积累相关的毒性风险。
