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Targeted CT imaging of human hepatocellular carcinoma using low-generation dendrimerentrapped gold nanoparticles modified with lactobionic acid

机译:低代树状大分子包裹的金纳米粒子经乳糖酸改性的人肝细胞靶向CT成像

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Development of cost-effective nanoscale contrast agents for targeted tumor computed tomography (CT) imaging remains a great challenge. Here, we report the synthesis of dendrimer-entrapped AuNPs (Au DENPs) using generation 2 poly(amidoamine) dendrimers pre-modified with fluorescein isothiocyanate via a thiourea linkage and lactobionic acid (LA) via a polyethylene glycol spacer as templates. The formed Au DENPs were characterized via different techniques and were used as a nanoprobe for targeted CT imaging of hepatocellular carcinoma (HCC). We show that the LA-modified Au DENPs with a mean Au core size of 1.8 nm are water-dispersible, colloidally stable under different temperatures (4-50 degrees C) and pH (5-8) conditions, and cytocompatible in the studied concentration range. Flow cytometry results reveal that the LA-Au DENPs are able to specifically target HepG2 cells (a human HCC cell line) overexpressing asialoglycoprotein receptors via a receptor-mediated targeting pathway. Importantly, the developed LA-Au DENPs can be used as a nanoprobe for targeted CT imaging of HepG2 cells in vitro and the xenografted tumor model in vivo. With the demonstrated organ compatibility, the developed LA-Au DENPs using low-generation dendrimers as templates can be a good candidate to be used as a highly efficient and cost-effective nanoprobe for targeted CT imaging of HCC.
机译:用于靶向肿瘤计算机断层扫描(CT)成像的具有成本效益的纳米级造影剂的开发仍然是巨大的挑战。在这里,我们报道了使用通过异硫氰酸荧光素经硫脲连接和以聚乙二醇间隔基为模板的乳糖酸(LA)预改性的第2代聚(酰胺胺)树状大分子,合成了树状大分子包裹的AuNPs(Au DENPs)。形成的金DENPs通过不同的技术进行了表征,并被用作针对肝细胞癌(HCC)的靶向CT成像的纳米探针。我们显示,平均Au核心尺寸为1.8 nm的LA修饰的Au DENPs是水分散性的,在不同温度(4-50摄氏度)和pH(5-8)条件下胶体稳定,并且在研究浓度下具有细胞相容性范围。流式细胞仪结果表明,LA-Au DENPs能够通过受体介导的靶向途径特异性靶向过度表达去唾液酸糖蛋白受体的HepG2细胞(人类HCC细胞系)。重要的是,已开发的LA-Au DENP可用作纳米探针,可用于体外HepG2细胞的靶向CT成像以及体内异种移植肿瘤模型。凭借已证明的器官相容性,使用低代树状聚合物作为模板开发的LA-Au DENPs可以作为用于HCC靶向CT成像的高效且具有成本效益的纳米探针。

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