Liposomes represent suitable tools for the diagnosis and treatment of a variety of diseases, including cancers. To study the role of the human epidermal growth factor receptor 2 (HER2) as target in cancer imaging and image-guided deliveries, liposomes were encapsulated with an intrinsically quenched concentration of a near-infrared fluorescent dye in their aqueous interior. This resulted in quenched liposomes (termed LipQ), that were fluorescent exclusively upon degradation, dye release, and activation. The liposomes carried an always-on green fluorescent phospholipid in the lipid layer to enable tracking of intact liposomes. Additionally, they were functionalized with single-chain antibody fragments directed to fibroblast activation protein (FAP), a marker of stromal fibroblasts of most epithelial cancers, and to HER2, whose overexpression in 20–30% of all breast cancers and many other cancer types is associated with a poor treatment outcome and relapse. We show that both monospecific (HER2-IL) and bispecific (Bi-FAP/HER2-IL) formulations are quenched and undergo HER2-dependent rapid uptake and cargo release in cultured target cells and tumor models in mice. Thereby, tumor fluorescence was retained in whole-body NIRF imaging for 32–48 h post-injection. Opposed to cell culture studies, Bi-FAP/HER2-IL-based live confocal microscopy of a high HER2-expressing tumor revealed nuclear delivery of the encapsulated dye. Thus, the liposomes have potentials for image-guided nuclear delivery of therapeutics, and also for intraoperative delineation of tumors, metastasis, and tumor margins.

中文翻译：

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具有HER2和FAP单链抗体片段的可活化脂质体的快速目标结合和货物释放揭示了将图像引导递送至肿瘤的潜力。

脂质体代表用于诊断和治疗包括癌症在内的多种疾病的合适工具。为了研究人类表皮生长因子受体2（HER2）作为靶标在癌症成像和图像引导的递送中的作用，将脂质体用内在淬灭浓度的近红外荧光染料包裹在其水性内部。这导致淬灭的脂质体（称为LipQ），仅在降解，染料释放和活化后才发荧光。脂质体在脂质层中携带始终在线的绿色荧光磷脂，以便能够追踪完整的脂质体。此外，它们还通过针对大多数上皮癌的基质成纤维细胞标志物成纤维细胞活化蛋白（FAP）的单链抗体片段和HER2功能化，其在所有乳腺癌和许多其他癌症类型中的20-30％的过度表达与治疗效果差和复发有关。我们显示单特异性（HER2-IL）和双特异性（Bi-FAP / HER2-IL）制剂被淬灭，并在培养的靶细胞和小鼠肿瘤模型中经历了HER2依赖性的快速摄取和货物释放。因此，注射后32–48 h，肿瘤荧光在全身NIRF成像中得以保留。与细胞培养研究相反，基于Bi-FAP / HER2-IL的高共表达HER2肿瘤的实时共聚焦显微镜显示了包封染料的核传递。因此，脂质体具有用于图像指导的治疗药物核传递的潜力，并且还具有在手术中描述肿瘤，转移和肿瘤边缘的潜力。