摘要
粒径小于5 nm的极小尺寸氧化铁纳米颗粒(ESIONPs)作为T_(1)加权磁共振成像(T_(1)-MRI)造影剂展现出巨大的发展前景.然而,具有良好生物相容性的ESIONPs的批量生产仍然难以实现.本研究通过特别设计的气/液混合相流体反应器结合共沉淀合成方法,实现了聚葡萄糖山梨醇羧甲基醚(PSC)包覆的ESIONPs的连续制备,且其粒径在1.8–4.0 nm范围内可控.在不同粒径的ESIONPs中,粒径为3.7 nm的ESIONPs具有最好的T_(1)-MRI造影效果,特别是在临床3 T磁共振扫描设备下具有高的r_(1)值(4.11(mmol L^(−1))^(−1)s^(−1))和低的r_(2)/r_(1)值(7.90),并且在水相、细胞和血管环境中均展现出良好的T_(1)-MRI对比效果.此外,PSC包覆的ESIONPs具有良好的生物安全性,在水相中具有良好的分散性和长期稳定性,有望成为临床可用的安全有效的T_(1)-MRI造影剂.
Extremely small-sized iron oxide nanoparticles(ESIONPs)with sizes less than 5 nm have shown great promise as T_(1)contrast agents for magnetic resonance imaging(MRI).However,their facile and scalable production with simultaneously endowed biocompatible surface chemistry remains difficult to be realized.In this study,by using the coprecipitation method implemented in a specially designed gas/liquid mixed phase fluidic reactor,polyglucose sorbitol carboxymethyether(PSC)coated ESIONPs were continuously synthesized with controllable particle sizes ranging from 1.8 to 4 nm.Among the differently sized ESIONPs,the 3.7-nm ESIONPs exhibit the best performance as T_(1)MRI contrast agent,featuring a high r_(1) value of 4.11(mmol L^(−1))^(−1)s^(−1)and low r_(2)/r_(1) ratio of 7.90 under a clinical 3 T MR scanning,as well as the excellent T_(1)MRI contrast effect in not only water but also the cellular environment and blood vessel.Furthermore,the ESIONPs possess long-term stability and good dispersity in aqueous dispersions,making them ideal candidates as safe and effective T_(1)-weighted MRI contrast agent for real clinical use.
作者
毛宇
李艳
臧凤超
于昊立
严森
宋青松
秦志国
孙剑飞
陈博
黄晓
顾宁
Yu Mao;Yan Li;Fengchao Zang;Haoli Yu;Sen Yan;Qingsong Song;Zhiguo Qin;Jianfei Sun;Bo Chen;Xiao Huang;Ning Gu(State Key Laboratory of Bioelectronics,Jiangsu Key Laboratory for Biomaterials and Devices,School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China;Jiangsu Key Laboratory of Molecular and Functional Imaging,Medical School,Southeast University,Nanjing 210096,China;State Key Laboratory of Flexible Electronics&Institute of Advanced Materials,Jiangsu National Synergistic Innovation Center for Advanced Materials,Nanjing Tech University,Nanjing 210096,China;Materials Science and Devices Institute,Suzhou University of Science and Technology,Suzhou 215009,China)
基金
supported by the grant received from the National Key Research and Development Program of China(2017YFA0104302)
the Key Project of the National Natural Science Foundation of China(NSFC,51832001)
the National Natural Science Innovative Research Group Project(61821002)
the Project of the National Natural Science Foundation of China(31800843)。