Wang Chengbin, Yan Chenglin, An Lu, Zhao Huifeng, Song Shaoli, Yang Shiping
The Key Laboratory of Resource Chemistry of the Ministry of Education, the Shanghai Key Laboratory of Rare Earth Functional Materials, and the Shanghai Municipal Education Committee Key Laboratory of Molecular Imaging Probes and Sensors, Shanghai Normal University, Shanghai, 200234, China.
Fudan Univ, Dept Nucl Med, Shanghai Canc Ctr, 270 Dongan Rd, Shanghai, 200032, China.
J Mater Chem B. 2021 Sep 29;9(37):7734-7740. doi: 10.1039/d1tb01018b.
Superparamagnetic iron oxide nanoparticles with high magnetization strength and good biological safety have been widely used as magnetic resonance imaging (MRI) contrast agents for tumors. However, the accuracy of tumor diagnosis is still low due to the lack of tumor targeting and the interference signals from normal tissues. Endogenous substances in tumor (such as high levels of GSH and pH) stimuli-responsive contrast agents could offer higher sensitivity for tumor diagnosis. Herein, based on the characteristic of overexpression of GSH in tumors, we propose an ultra-small FeO assembly as an endogenous GSH responsive MRI contrast agent. The ultra-small superparamagnetic FeO are bonded to the crosslinker cystamine to synthesize FeO nanoclusters, which exhibit a imaging effect. When the contrast agent reaches the tumor tissue, the disulfide bond in cystamine is induced by GSH to break, the FeO nanoclusters are disassembled into ultra-small FeO nanoparticles, and the relaxation signal changes from to , which is helpful for accurate diagnosis of tumors. experiments have shown that FeO nanoclusters can rapidly respond to overexpressed GSH in tumor sites for / switchable imaging. This work not only designed an endogenous GSH responsive platform through simple synthesis methods, but also improved the accuracy of tumor diagnosis through the transformation of / MRI signals.
具有高磁化强度和良好生物安全性的超顺磁性氧化铁纳米颗粒已被广泛用作肿瘤的磁共振成像(MRI)造影剂。然而,由于缺乏肿瘤靶向性以及来自正常组织的干扰信号,肿瘤诊断的准确性仍然较低。肿瘤中的内源性物质(如高水平的谷胱甘肽和pH值)刺激响应型造影剂可为肿瘤诊断提供更高的灵敏度。在此,基于肿瘤中谷胱甘肽过表达的特性,我们提出一种超小的FeO聚集体作为内源性谷胱甘肽响应型MRI造影剂。将超小的超顺磁性FeO与交联剂胱胺结合以合成FeO纳米簇,其呈现出一种成像效果。当造影剂到达肿瘤组织时,胱胺中的二硫键被谷胱甘肽诱导断裂,FeO纳米簇分解成超小的FeO纳米颗粒,弛豫信号从 变为 ,这有助于肿瘤的准确诊断。实验表明,FeO纳米簇可以快速响应肿瘤部位过表达的谷胱甘肽以进行 / 可切换成像。这项工作不仅通过简单的合成方法设计了一个内源性谷胱甘肽响应平台,还通过 / MRI信号的转变提高了肿瘤诊断的准确性。