Huang Lixia, Yan Chenggong, Cui Danting, Yan Yichen, Liu Xiang, Lu Xinwei, Tan Xiangliang, Lu Xiaodan, Xu Jun, Xu Yikai, Liu Ruiyuan
Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Radiology, Guangdong Provincial Traditional Chinese Medical Hospital, Guangzhou, 510120, China.
Macromol Biosci. 2015 Jun;15(6):788-98. doi: 10.1002/mabi.201400403. Epub 2015 Feb 13.
Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.
氮氧化物作为用于肿瘤检测的磁共振成像（MRI）造影剂具有巨大潜力。通过相应取代乙炔的复分解聚合反应，合成了含有2,2,6,6-四甲基哌啶氧基（TEMPO）和聚乙二醇的聚乙炔，用于肿瘤的靶向双模态MRI/光学成像。聚乙炔中的聚乙二醇能使羧基荧光素和叶酸（FA）与羟基共价结合，从而开发出靶向多功能有机自由基造影剂（ORCA）。体外研究证实了靶向ORCA（PA-TEMPO-FI-FA）具有出色的结合特异性以及随后增强的细胞内化能力，且无细胞毒性。体内T1加权MRI显示PA-TEMPO-FI-FA具有主动肿瘤靶向能力，可在荷HeLa肿瘤小鼠中产生特异性对比增强。此外，纵向光学成像显示注射PA-TEMPO-FI-FA 1小时后肿瘤有高蓄积。这些结果表明，多功能ORCA可为进一步的分子成像引导癌症治疗提供肿瘤靶向递送平台。
