Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Bioorg Chem. 2022 Aug;125:105827. doi: 10.1016/j.bioorg.2022.105827. Epub 2022 May 5.
Hybridimagingtechnology has the potential to provide reliable imagingand accurate detection of cancer cells by combining the advantages and overcoming the shortages of various clinical imaging tools. Nanomaterials with unique targeting properties and their small size have improved biomedical imaging. Indeed, their small size determines local contrast agent concentrations in tumors by enhanced permeability and retention (EPR) effect. In this work, amino-modified silica-coated Gadolinium-Copper Nanoclusters were fabricated and conjugated to AS1411 aptamer (Apt-ASGCuNCs) and radiolabeled with technetium-99 m (Tc) for in vivo fluorescence imaging, magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). The synthesized nanoconjugate was fully characterized by transmission electron microscopy (TEM), element mapping, fluorescence spectroscopy, and Fourier-transform infrared spectroscopy. Moreover, XTT assay, and apoptosis and necrosis methods were applied to study toxicity. Radiochemical yield was calculated 93% that revealed a great potential for complex formation between Apt-ASGCuNCs and TcO. Also, good stability of Tc-Apt-ASGCuNCs was found in the human serum up to 4 h. Both Apt-ASGCuNCs and Tc-Apt-ASGCuNCs indicated a considerable tumor-targeting in in vivo fluorescence imaging, MRI and SPECT with 4T1 tumor-bearing BALB/c mice. The biodistribution results showed no undesirable accumulation of Tc-Apt-ASGCuNCs in the liver, and spleen as it circulated freely in the blood pool. Meanwhile, Tc-Apt-ASGCuNCs were removed from the body through the renal clearance system, making it more convenient for future multimodality imaging applications.
混合成像技术通过结合各种临床成像工具的优势并克服其缺点,有可能提供可靠的成像和对癌细胞的准确检测。具有独特靶向特性和小尺寸的纳米材料改善了生物医学成像。事实上,它们的小尺寸通过增强的通透性和保留(EPR)效应决定了肿瘤中局部造影剂的浓度。在这项工作中,制备了氨基修饰的硅涂层的钆-铜纳米团簇,并将其与 AS1411 适体(Apt-ASGCuNCs)偶联,并放射性标记锝-99(Tc),用于体内荧光成像、磁共振成像(MRI)和单光子发射计算机断层扫描(SPECT)。通过透射电子显微镜(TEM)、元素映射、荧光光谱和傅里叶变换红外光谱对合成的纳米复合物进行了全面表征。此外,还应用 XTT 测定法、凋亡和坏死方法研究了毒性。放射性化学产率计算为 93%,表明 Apt-ASGCuNCs 和 TcO 之间形成复合物的潜力巨大。此外,在人血清中发现 Tc-Apt-ASGCuNCs 具有良好的稳定性,在 4 小时内都没有发现其复合物的稳定性降低。Apt-ASGCuNCs 和 Tc-Apt-ASGCuNCs 均在 4T1 荷瘤 BALB/c 小鼠的体内荧光成像、MRI 和 SPECT 中显示出相当的肿瘤靶向性。生物分布结果表明,Tc-Apt-ASGCuNCs 不会在肝脏和脾脏中积聚,因为它在血液池中自由循环。同时,Tc-Apt-ASGCuNCs 通过肾脏清除系统从体内排出,这使其更便于未来的多模态成像应用。