Development of novel activable dual-mode T1/T2-weighted magnetic resonance (MR) contrast agents with the same composition for dynamic precision imaging of tumors has been a challenging task. Here, we demonstrated a strategy to prepare clustered Fe3O4 nanoparticles (NPs) with redox-responsiveness to tumor microenvironment to achieve switchable T2/T1-weighted dual-mode MR imaging applications. In this study, we first synthesized ultrasmall Fe3O4 NPs with an average size of 3.3 nm and an r1 relaxivity of 4.3 mM-1 s-1, and then cross-linked the single Fe3O4 NPs using cystamine dihydrochloride (Cys) to form clustered Fe3O4/Cys NPs. The Fe3O4 nanoclusters (NCs) possess desirable colloidal stability, cytocompatibility, high r2 relaxivity (26.4 mM-1 s-1), and improved cellular uptake efficiency. Importantly, with the redox-responsiveness of the disulfide bond of Cys, the Fe3O4 NCs can be dissociated to form single particles under a reducing condition, hence displaying a switchable T2/T1-weighted MR imaging property that can be utilized for dynamic precision imaging of cancer cells in vitro and a subcutaneous tumor model in vivo due to the reductive intracellular environment of cancer cells and the tumor microenvironment. With the tumor reductive microenvironment-mediated switching of T2 to T1 MR effect and the ultrasmall size of the single particles that can pass through the kidney filter, the developed Fe3O4 NCs may be used as a promising switchable T2/T1 dual-mode MR contrast agent for precision imaging of different biosystems.

中文翻译：

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用于可切换T2 / T1加权磁共振成像应用的氧化还原敏感簇状超小氧化铁纳米粒子。

具有相同组成的新型可激活双模式T1 / T2加权磁共振（MR）造影剂用于肿瘤动态精确成像的开发一直是一项艰巨的任务。在这里，我们展示了一种制备对肿瘤微环境具有氧化还原反应性的簇状Fe3O4纳米颗粒（NPs）的策略，以实现可切换的T2 / T1加权双模MR成像应用。在这项研究中，我们首先合成了平均尺寸为3.3 nm，r1弛豫度为4.3 mM-1 s-1的超小Fe3O4 NP，然后使用半胱胺盐酸盐（Cys）交联了单个Fe3O4 NP形成簇状Fe3O4 /半胱氨酸NPs。Fe3O4纳米簇（NCs）具有理想的胶体稳定性，细胞相容性，高r2弛豫性（26.4 mM-1 s-1）和提高的细胞吸收效率。重要的，通过Cys二硫键的氧化还原响应性，Fe3O4 NCs可以在还原条件下解离形成单个颗粒，因此显示出可切换的T2 / T1加权MR成像性能，可用于癌细胞的动态精密成像由于癌细胞的还原性细胞内环境和肿瘤微环境，体外和皮下肿瘤模型在体内。随着肿瘤还原性微环境介导的T2到T1 MR效应的转换以及可以通过肾脏滤器的单个颗粒的超小尺寸，开发的Fe3O4 NCs可以用作有前途的可切换T2 / T1双模MR造影剂用于不同生物系统的精确成像。因此，由于癌细胞的还原性细胞内环境和肿瘤微环境，因此显示出可切换的T2 / T1加权MR成像特性，可用于体外动态精密成像和体内皮下肿瘤模型。随着肿瘤还原性微环境介导的T2到T1 MR效应的转换以及可以通过肾脏滤器的单个颗粒的超小尺寸，开发的Fe3O4 NCs可以用作有前途的可切换T2 / T1双模MR造影剂用于不同生物系统的精确成像。因此，由于癌细胞的还原性细胞内环境和肿瘤微环境，因此显示出可切换的T2 / T1加权MR成像特性，可用于体外动态精密成像和体内皮下肿瘤模型。随着肿瘤还原性微环境介导的T2到T1 MR效应的转换以及可以通过肾脏滤器的单个颗粒的超小尺寸，开发的Fe3O4 NCs可以用作有前途的可切换T2 / T1双模MR造影剂用于不同生物系统的精确成像。