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PEGylated Amphiphilic Gd-DOTA Backboned-Bound Branched Polymers as Magnetic Resonance Imaging Contrast Agents
Biomacromolecules ( IF 5.5 ) Pub Date : 2023-11-09 , DOI: 10.1021/acs.biomac.3c00987 Shengxiang Fu 1, 2 , Zhongyuan Cai 1 , Li Liu 1 , Xiaomin Fu 1 , Chunchao Xia 3 , Su Lui 3 , Qiyong Gong 2, 4 , Bin Song 3 , Hua Ai 1, 3
Biomacromolecules ( IF 5.5 ) Pub Date : 2023-11-09 , DOI: 10.1021/acs.biomac.3c00987 Shengxiang Fu 1, 2 , Zhongyuan Cai 1 , Li Liu 1 , Xiaomin Fu 1 , Chunchao Xia 3 , Su Lui 3 , Qiyong Gong 2, 4 , Bin Song 3 , Hua Ai 1, 3
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MRI contrast agents with high kinetic stability and relaxivity are the key objectives in the field. We previously reported that Gd-DOTA backboned-bound branched polymers possess high kinetic stability and significantly increased T1 relaxivity than traditional branched polymer contrast agents. In this work, non-PEGylated and PEGylated amphiphilic Gd-DOTA backboned-bound branched polymers [P(GdDOTA-C6), P(GdDOTA-C10), mPEG-P(GdDOTA-C6), and mPEG-P(GdDOTA-C10)] were obtained by sequential introduction of rigid carbon chains (1,6-hexamethylenediamine or 1,10-diaminodecane) and mPEG into the structure of Gd-DOTA backboned-bound branched polymers. It is found that the introduction of both rigid carbon chains, especially the longer one, and mPEG can increase the kinetic stability and T1 relaxivity of Gd-DOTA backboned-bound branched polymers. Among them, mPEG-P(GdDOTA-C10) possesses the highest kinetic stability (significantly higher than those of linear Gd-DTPA and cyclic Gd-DOTA-butrol) and T1 relaxivity (42.9 mM–1 s–1, 1.5 T), 11 times that of Gd-DOTA and 1.4 times that of previously reported Gd-DOTA backboned-bound branched polymers. In addition, mPEG-P(GdDOTA-C10) showed excellent MRA effect in cardiovascular and hepatic vessels at a dose (0.025 or 0.05 mmol Gd/kg BW) far below the clinical range (0.1–0.3 mmol Gd/kg BW). Overall, effective branched-polymer-based contrast agents can be obtained by a strategy in which rigid carbon chains and PEG were introduced into the structure of Gd-DOTA backbone-bound branched polymers, resulting in excellent kinetic stability and enhanced T1 relaxivity.
中文翻译：
聚乙二醇化两亲性 Gd-DOTA 主链支化聚合物作为磁共振成像造影剂
具有高动力学稳定性和弛豫性的 MRI 造影剂是该领域的关键目标。我们之前报道过，Gd-DOTA骨架结合的支化聚合物具有高动力学稳定性，并且比传统支化聚合物造影剂显着提高了T 1弛豫率。在这项工作中，非聚乙二醇化和聚乙二醇化两亲性 Gd-DOTA 主链结合支化聚合物 [P(GdDOTA-C 6 )、P(GdDOTA-C 10 )、mPEG-P(GdDOTA-C 6 ) 和 mPEG-P( GdDOTA-C 10 )]是通过将刚性碳链（1,6-六亚甲基二胺或1,10-二氨基癸烷）和mPEG依次引入Gd-DOTA主链结合的支化聚合物的结构中获得的。研究发现，引入两条刚性碳链（尤其是较长的碳链）和mPEG可以提高Gd-DOTA主链结合的支化聚合物的动力学稳定性和T 1弛豫率。其中，mPEG-P(GdDOTA-C 10 )具有最高的动力学稳定性（显着高于线性Gd-DTPA和环状Gd-DOTA-buttrol）和T 1弛豫率（42.9 mM –1 s –1 , 1.5 T） ），是 Gd-DOTA 的 11 倍，是之前报道的 Gd-DOTA 主链结合支化聚合物的 1.4 倍。此外，mPEG-P(GdDOTA-C 10 )在远低于临床范围(0.1-0.3 mmol Gd/kg BW)的剂量(0.025或0.05 mmol Gd/kg BW)下在心血管和肝血管中表现出优异的MRA效果。 总体而言，通过将刚性碳链和PEG引入到Gd-DOTA主链结合的支化聚合物结构中的策略可以获得有效的基于支化聚合物的造影剂，从而获得优异的动力学稳定性和增强的T 1弛豫率。
更新日期：2023-11-09
中文翻译：
聚乙二醇化两亲性 Gd-DOTA 主链支化聚合物作为磁共振成像造影剂
具有高动力学稳定性和弛豫性的 MRI 造影剂是该领域的关键目标。我们之前报道过，Gd-DOTA骨架结合的支化聚合物具有高动力学稳定性，并且比传统支化聚合物造影剂显着提高了T 1弛豫率。在这项工作中，非聚乙二醇化和聚乙二醇化两亲性 Gd-DOTA 主链结合支化聚合物 [P(GdDOTA-C 6 )、P(GdDOTA-C 10 )、mPEG-P(GdDOTA-C 6 ) 和 mPEG-P( GdDOTA-C 10 )]是通过将刚性碳链（1,6-六亚甲基二胺或1,10-二氨基癸烷）和mPEG依次引入Gd-DOTA主链结合的支化聚合物的结构中获得的。研究发现，引入两条刚性碳链（尤其是较长的碳链）和mPEG可以提高Gd-DOTA主链结合的支化聚合物的动力学稳定性和T 1弛豫率。其中，mPEG-P(GdDOTA-C 10 )具有最高的动力学稳定性（显着高于线性Gd-DTPA和环状Gd-DOTA-buttrol）和T 1弛豫率（42.9 mM –1 s –1 , 1.5 T） ），是 Gd-DOTA 的 11 倍，是之前报道的 Gd-DOTA 主链结合支化聚合物的 1.4 倍。此外，mPEG-P(GdDOTA-C 10 )在远低于临床范围(0.1-0.3 mmol Gd/kg BW)的剂量(0.025或0.05 mmol Gd/kg BW)下在心血管和肝血管中表现出优异的MRA效果。 总体而言，通过将刚性碳链和PEG引入到Gd-DOTA主链结合的支化聚合物结构中的策略可以获得有效的基于支化聚合物的造影剂，从而获得优异的动力学稳定性和增强的T 1弛豫率。
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