Luo Minrui, Bailey Matthew D, Kim Hyun, Lei Yiqing, Meade Thomas J
Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, Illinois 60208, United States.
ACS Appl Mater Interfaces. 2025 May 14;17(19):28000-28011. doi: 10.1021/acsami.5c05524. Epub 2025 May 5.
Liver cancer remains one of the most lethal malignancies worldwide, primarily due to limited diagnostic and therapeutic strategies. Biological imaging agents capable of selective accumulation in cancerous liver tissue offer a promising route for earlier detection and improved patient outcomes. In this work, we synthesized and characterized alkaline phosphatase (ALP)-targeted, gadolinium-labeled gold nanoparticles (AuNPs) designed for simultaneous detection using magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence (Fl) microscopy. The synthesized AuNPs feature 13 nm gold cores functionalized with ALP-binding ligands and Gd(III)-macrocycles. Characterization by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy (EDX) confirmed successful functionalization. During the functionalization process, variations in Gd(III) loading, surface packing density, and relaxivity were observed; however, high reproducibility was achieved when including methanol during the AuNP labeling protocol. studies with HepG2 liver cancer and HEK293 kidney cells demonstrated selective cellular uptake in relation to cellular ALP expression levels. Optimized uptake conditions demonstrated 10-fold increase in Gd(III) internalization into HepG2 versus HEK293 cells. Further imaging by scanning electron microscopy (SEM) and TEM on thinly sliced cell samples verified the intracellular localization of these nanoparticles. Collectively, these findings underscore the potential of ALP-targeted, gadolinium-labeled AuNPs as a versatile multimodal imaging platform for the early detection of liver cancer.
肝癌仍然是全球最致命的恶性肿瘤之一，主要原因是诊断和治疗策略有限。能够在癌性肝组织中选择性聚集的生物成像剂为早期检测和改善患者预后提供了一条有前景的途径。在这项工作中，我们合成并表征了靶向碱性磷酸酶（ALP）、钆标记的金纳米颗粒（AuNP），其设计用于通过磁共振成像（MRI）、计算机断层扫描（CT）和荧光（Fl）显微镜进行同步检测。合成的AuNP具有13纳米的金核，用ALP结合配体和钆（III）大环进行了功能化修饰。通过紫外可见（UV-vis）光谱、动态光散射（DLS）、透射电子显微镜（TEM）和能量色散X射线光谱（EDX）进行的表征证实了功能化的成功。在功能化过程中，观察到钆（III）负载量、表面堆积密度和弛豫率的变化；然而，在AuNP标记方案中加入甲醇时，实现了高重现性。对肝癌HepG2细胞和肾HEK293细胞的研究表明，细胞摄取与细胞ALP表达水平相关。优化的摄取条件表明，与HEK293细胞相比，HepG2细胞中钆（III）的内化增加了10倍。通过扫描电子显微镜（SEM）和TEM对薄切片细胞样本进行的进一步成像证实了这些纳米颗粒的细胞内定位。总的来说，这些发现强调了靶向ALP、钆标记的AuNP作为一种用于肝癌早期检测的通用多模态成像平台的潜力。
