CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
J Mater Chem B. 2021 Feb 25;9(7):1821-1832. doi: 10.1039/d0tb02411b.
Magnetic resonance imaging (MRI) contrast agents (CAs) have drawn increasing attention in cancer diagnosis. However, since the signals they generate are always "on" and may bring interfering background signals to the region of interest, their selectivity and sensitivity need further improvement. Herein, extremely small iron oxide nanoparticles (ESIONPs) conjugated through a disulfide bond with polyethylene glycol (PEG) that is terminally modified with folic acid (FA), namely ESIONPs-s-s-PEG-FA, were designed and synthesized to target tumor tissues and selectively activate the T2 MRI contrast effect in the reducing environment of tumor cells. Due to the breakage of disulfide bonds by the high glutathione (GSH) concentration in tumor cells, the hydrophilic PEG chains detached from the surface of ESIONPs, which led to the aggregation of ESIONPs and the activation of the T2 contrast effect. In vitro results showed that ESIONPs-s-s-PEG-FA could effectively target tumors to assemble in the reductive environment and switch from a T1 contrast agent (CA) to a T2 one. Furthermore, MRI in tumor-bearing mice also indicated the obvious targeting capacity and the "turn on" of the T2 contrast effect. In addition, the results of the biosafety assay suggest that the tumor-targeted T1/T2 switchable CA is equipped with favorable biocompatibility for cancer diagnosis.
磁共振成像（MRI）造影剂（CA）在癌症诊断中受到越来越多的关注。然而，由于它们产生的信号始终“开启”，并且可能给感兴趣的区域带来干扰背景信号，因此需要进一步提高其选择性和敏感性。在此，设计并合成了通过二硫键与末端修饰有叶酸（FA）的聚乙二醇（PEG）连接的超小氧化铁纳米颗粒（ESIONPs），即 ESIONPs-s-s-PEG-FA，以靶向肿瘤组织并选择性地激活肿瘤细胞还原环境中的 T2 MRI 对比效应。由于肿瘤细胞中高浓度谷胱甘肽（GSH）使二硫键断裂，亲水性 PEG 链从 ESIONPs 表面脱落，导致 ESIONPs 聚集并激活 T2 对比效应。体外结果表明，ESIONPs-s-s-PEG-FA 可以有效地靶向肿瘤，在还原环境中组装，并从 T1 造影剂（CA）转变为 T2 造影剂。此外，荷瘤小鼠的 MRI 也表明了明显的靶向能力和 T2 对比效应的“开启”。此外，生物安全性检测结果表明，肿瘤靶向 T1/T2 可切换 CA 具有良好的用于癌症诊断的生物相容性。
