具有琥珀酰化肝素单层涂层的超紧凑型氧化铁纳米颗粒:一类用于高场磁共振成像的新型可经肾脏清除且无毒的造影剂。

Ultracompact Iron Oxide Nanoparticles with a Monolayer Coating of Succinylated Heparin: A New Class of Renal-Clearable and Nontoxic T Agents for High-Field MRI.

作者信息

Xie Manman, Wang Ziyang, Lu Qian, Nie Shuming, Butch Christopher J, Wang Yiqing, Dai Bo

机构信息

Department of Biomedical Engineering, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing 210093, China.

Department of Biomedical Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

出版信息

ACS Appl Mater Interfaces. 2020 Dec 2;12(48):53994-54004. doi: 10.1021/acsami.0c12454. Epub 2020 Nov 19.

Abstract

Herein, we present a new magnetic iron oxide nanoparticle (MION) with a succinylated heparin monolayer coating, which exhibits the highest T relaxivity at 7 T and the lowest / reported for any MION at these high-field conditions. While the recent proliferation of 7 T MRI instruments in hospitals worldwide has enabled widespread access to higher quality, more finely detailed, diagnostic imaging, clinically available contrast agents have not kept pace due to the general phenomenon of reduced efficacy of T relaxation as magnetic field strength is increased. Development of new MION agents is one strategy to address this need, and to this end, we demonstrate the magnetic properties of the MIONs reported here to extend to applications, providing greatly increased contrast in tumor imaging in a murine xenograft subject at 7 T. While MION-based contrast agents can have side effects in clinical application, these are generally thought to be less than those of gadolinium-based agents and here are further reduced by the small size allowing direct glomerular filtration from the blood followed by renal-excretion. Finally, we show the succinylated heparin monolayer coating to provide class leading magnetic properties over a homologous series of particles with core size ranging from 2 to 18 nm and show the properties to be strongly related to the surface area. We suggest the increased porosity and hydrophilicity of the coating to increase water accessibility to the surface resulting in the increased magnetic properties.

摘要

在此,我们展示了一种具有琥珀酰化肝素单层涂层的新型磁性氧化铁纳米颗粒(MION),它在7 T时表现出最高的T弛豫率,且在这些高场条件下是所有已报道的MION中最低的。虽然最近全球医院中7 T MRI仪器的激增使得人们能够广泛获得更高质量、更精细的诊断成像,但由于随着磁场强度增加T弛豫效率普遍降低这一现象,临床上可用的造影剂并未跟上步伐。开发新型MION剂是满足这一需求的一种策略,为此,我们证明了此处报道的MION的磁性可扩展至应用领域,在7 T的小鼠异种移植模型的肿瘤成像中提供显著增强的对比度。虽然基于MION的造影剂在临床应用中可能有副作用,但一般认为这些副作用小于基于钆的造影剂,并且此处由于颗粒尺寸小,可直接从血液中进行肾小球滤过然后经肾脏排泄,副作用进一步降低。最后,我们表明琥珀酰化肝素单层涂层在一系列核心尺寸范围为2至18 nm的同源颗粒中提供了一流的磁性,并表明这些性质与表面积密切相关。我们认为涂层孔隙率和亲水性的增加会增加水与表面的接触,从而导致磁性增强。

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