采用流体反应器连续制备可用于T_(1)加权磁共振成像的极小尺寸氧化铁纳米颗粒

Continuous synthesis of extremely small-sized iron oxide nanoparticles used for T_(1)-weighted magnetic resonance imaging via a fluidic reactor

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.