Xue Xiangdong, Bo Ruonan, Qu Haijing, Jia Bei, Xiao Wenwu, Yuan Ye, Vapniarsky Natalia, Lindstrom Aaron, Wu Hao, Zhang Dalin, Li Longmeng, Ricci Marina, Ma Zhao, Zhu Zheng, Lin Tzu-Yin, Louie Angelique Y, Li Yuanpei
Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA.
Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, 95817, USA; School of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, PR China.
Biomaterials. 2020 Oct;257:120234. doi: 10.1016/j.biomaterials.2020.120234. Epub 2020 Jul 15.
Gadolinium-based contrast agents (GBCAs) are the most widely used T contrast agents for magnetic resonance imaging (MRI) and have achieved remarkable success in clinical cancer diagnosis. However, GBCAs could cause severe nephrogenic systemic fibrosis to patients with renal insufficiency. Nevertheless, GBCAs are quickly excreted from the kidneys, which shortens their imaging window and prevents long-term monitoring of the disease per injection. Herein, a nephrotoxicity-free T MRI contrast agent is developed by coordinating ferric iron into a telodendritic, micellar nanostructure. This new nano-enabled, iron-based contrast agent (nIBCA) not only can reduce the renal accumulation and relieve the kidney burden, but also exhibit a significantly higher tumor to noise ratio (TNR) for cancer diagnosis. In comparison with Magnevist (a clinical-used GBCA), Magnevist induces obvious nephrotoxicity while nIBCA does not, indicating that such a novel contrast agent may be applicable to renally compromised patients requiring a contrast-enhanced MRI. The nIBCA could precisely image subcutaneous brain tumors in a mouse model and the effective imaging window lasted for at least 24 h. The nIBCA also precisely highlights the intracranial brain tumor with high TNR. The nIBCA presents a potential alternative to GBCAs as it has superior biocompatibility, high TNR and effective imaging window.
钆基造影剂（GBCAs）是磁共振成像（MRI）中使用最广泛的T造影剂，在临床癌症诊断中取得了显著成功。然而，GBCAs可能会给肾功能不全患者造成严重的肾源性系统性纤维化。尽管如此，GBCAs会迅速从肾脏排出，这缩短了它们的成像窗口，并且每次注射后无法对疾病进行长期监测。在此，通过将三价铁配位到端树突状胶束纳米结构中，开发出了一种无肾毒性的T MRI造影剂。这种新型的基于纳米技术的铁基造影剂（nIBCA）不仅可以减少在肾脏的蓄积并减轻肾脏负担，而且在癌症诊断中表现出显著更高的肿瘤与噪声比（TNR）。与临床使用的GBCA造影剂马根维显相比，马根维显会诱发明显的肾毒性，而nIBCA则不会，这表明这种新型造影剂可能适用于需要进行增强MRI检查的肾功能受损患者。nIBCA可以在小鼠模型中精确成像皮下脑肿瘤，有效的成像窗口持续至少24小时。nIBCA还能以高TNR精确突出显示颅内脑肿瘤。nIBCA具有优异的生物相容性、高TNR和有效的成像窗口，是GBCAs的一种潜在替代品。
