Purpose: Gd-encapsulated carbonaceous dots (Gd@C-dots) have excellent stability and magnetic properties without free Gd leakage, therefore they can be considered as a safe alternative T1 contrast agent to commonly used Gd complexes. To improve their potential for cancer diagnosis and treatment, affibody-modified Gd@C-dots targeting non-small-cell lung cancer (NSCLC) EGFR-positive tumors with enhanced renal clearance were developed and synthesized.
Materials and Methods: Gd@C-dots were developed and modified with Ac-Cys-Z_EGFR:1907 through EDC/NHS. The size, morphology, and optical properties of the Gd@C-dots and Gd@C-dots-Cys-Z_EGFR:1907 were characterized. Targeting ability was evaluated by in vitro and in vivo experiments, respectively. Residual gadolinium concentration in major organs was detected with confocal imaging and inductively coupled plasma mass spectrometry (ICP-MS) ex vivo. H&E staining was used to assess the morphology of these organs.
Results: Gd@C-dots with nearly 20 nm in diameter were developed and modified with Ac-Cys-Z_EGFR:1907. EGFR expression in HCC827 cells was higher than NCI-H520. In cell uptake assays, EGFR-expressing HCC827 cells exhibited significant MR T1WI signal enhancement when compared to NCI-H520 cells. Cellular uptake of Gd@C-dots-Cys-Z_EGFR:1907 was reduced, when Ac-Cys-Z_EGFR:1907 was added. In vivo targeting experiments showed that the probe signal was significantly higher in HCC827 than NCI-H520 xenografts at 1 h after injection. In contrast to Gd@C-dots, Gd@C-dots-Cys-Z_EGFR:1907 nanoparticles can be efficiently excreted through renal clearance. No morphological changes were observed by H&E staining in the major organs after injection of Gd@C-dots-Cys-Z_EGFR:1907.
Conclusion: Gd@C-dots-Cys-Z_EGFR:1907 is a high-affinity EGFR-targeting probe with efficient renal clearance and is therefore a promising contrast agent for clinical applications such as diagnosis and treatment of NSCLC EGFR-positive malignant tumors.

Keywords: Gd@C-dots, EGFR, MRI, nanoparticles, efficient renal clearance


中文翻译：

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具有高效肾清除功能的 Affibody 修饰的 Gd@C-Dots 用于增强非小细胞肺癌中 EGFR 表达的 MRI。

目的： Gd包封的碳质点（Gd@C-dots）具有优异的稳定性和磁性，无游离Gd泄漏，因此可以作为常用Gd配合物的安全替代T1造影剂。为了提高其在癌症诊断和治疗方面的潜力，开发并合成了靶向非小细胞肺癌 (NSCLC) EGFR 阳性肿瘤的 affibody 修饰的 Gd@C-dots，具有增强的肾清除率。
材料和方法： Gd@C-dots 是通过 EDC/NHS用 Ac-Cys-Z _{EGFR:1907开发和修饰的。}Gd@C-dots 和 Gd@C-dots-Cys-Z _{EGFR:1907的尺寸、形态和光学性质}进行了表征。靶向能力分别通过体外和体内实验进行评估。通过离体共聚焦成像和电感耦合等离子体质谱 (ICP-MS) 检测主要器官中的残留钆浓度。H&E 染色用于评估这些器官的形态。
结果：用Ac-Cys-Z _EGFR:1907开发和修饰了直径近20 nm的Gd@C-dots 。HCC827细胞中EGFR的表达高于NCI-H520。在细胞摄取测定中，与 NCI-H520 细胞相比，表达 EGFR 的 HCC827 细胞表现出显着的 MR T1WI 信号增强。_{Gd@C-dots-Cys-Z EGFR:1907}的细胞摄取减少，当 Ac-Cys-Z _EGFR:1907加入。体内靶向实验表明，在注射后 1 小时，HCC827 中的探针信号显着高于 NCI-H520 异种移植物。与 Gd@C-dots 相比，Gd@C-dots-Cys-Z _EGFR:1907纳米颗粒可以通过肾脏清除有效地排泄。_{注射 Gd@C-dots-Cys-Z EGFR:1907}后主要器官的 H&E 染色未观察到形态学变化。
结论： Gd@C-dots-Cys-Z _EGFR:1907是一种高亲和力的EGFR靶向探针，具有高效的肾清除率，是一种很有前景的造影剂，可用于NSCLC EGFR阳性恶性肿瘤的诊断和治疗等临床应用。

关键词： Gd@C-dots，EGFR，MRI，纳米颗粒，有效肾清除率