Tumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with the transgenic-targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic αv integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well suited as T2 contrast agents, while exhibiting an increased binding compared to the binding in wild-type magnetosomes.

中文翻译：

---

用于肿瘤成像的靶向磁共振成像造影剂的遗传编码。

肿瘤选择性造影剂有可能帮助使用诸如磁共振成像 (MRI) 等非侵入性成像方式诊断和治疗癌症。这种造影剂可以由磁性纳米粒子组成，该纳米粒子结合了对肿瘤环境特有的线索作出反应的功能。已经研究了通过基因工程改造趋磁细菌来展示肽，作为一种生产造影剂的手段，这种造影剂将磁小体的强大图像对比度效应与展示在其表面上的转基因靶向肽相结合。这项工作报告了磁性纳米粒子的首次使用，该纳米粒子显示基因编码的 pH 低插入肽 (pHLIP)，这是一种旨在通过靶向与肿瘤相关的细胞外酸度来增强 MRI 对比度的长肽。为了证明这个多功能平台的模块化以通过基因工程整合不同的靶向配体，我们还将环状 αv 整合素结合肽 iRGD 整合到单独的磁小体中。具体来说，我们研究了它们在体外和体内增强结合和肿瘤成像的潜力。我们的实验表明，这些定制的磁小体保留了它们的磁性，使其非常适合作为 T2 造影剂，同时与野生型磁小体中的结合相比，结合表现出更高的结合。