State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, 210093, PR China; Institute of Materials Engineering, National Laboratory of Solid State Microstructure, College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, PR China.
Institute of Materials Engineering, National Laboratory of Solid State Microstructure, College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, PR China.
Biomaterials. 2015 May;51:194-207. doi: 10.1016/j.biomaterials.2015.02.019. Epub 2015 Feb 19.
Development of non-invasive assay for the accurate diagnosis of progressive liver diseases (e.g., fatty liver and hepatocellular carcinoma (HCC)) is of great clinical significance and remains to be a big challenge. Herein, we reported the synthesis of strawberry-like Fe3O4-Au hybrid nanoparticles at room temperature that simultaneously exhibited fluorescence, enhanced X-ray attenuation, and magnetic properties. The results of in vitro fluorescence assay showed that the nanoparticles had significant photo-stability and could avoid the endosome degradation in cells. The in vivo imaging of normal mice demonstrated that the Fe3O4-Au nanoparticles provided 34.61-fold contrast enhancement under magnetic resonance (MR) guidance 15 min post the administration. Computed tomography (CT) measurements showed that the highest Hounsfield Unit (HU) was 174 at 30 min post the injection of Fe3O4-Au nanoparticles. In vivo performance of the Fe3O4-Au nanoparticles was further evaluated in rat models bearing three different liver diseases. For the fatty liver model, nearly homogeneous contrast enhancement was observed under both MR (highest contrast ratio 47.33) and CT (from 19 HU to 72 HU) guidances without the occurrences of focal nodules or dysfunction. For the cirrhotic liver and HCC, pronounced enhancement under MR and CT guidance could be seen in liver parenchyma with highlighted lesions after Fe3O4-Au injection. Furthermore, pathological, hematological and biochemical analysis revealed the absence of acute and chronic toxicity, confirming the biocompatibility of our platform for in vivo applications. Collectively, These Fe3O4-Au nanoparticles showed great promise as a candidate for multi-modality bio-imaging.
开发用于准确诊断进行性肝脏疾病(例如脂肪肝和肝细胞癌(HCC))的非侵入性检测方法具有重要的临床意义,仍然是一个巨大的挑战。在此,我们报告了在室温下合成草莓状 Fe3O4-Au 杂化纳米粒子,其同时具有荧光增强、X 射线衰减增强和磁性。体外荧光检测结果表明,该纳米粒子具有显著的光稳定性,可以避免细胞内的内涵体降解。正常小鼠的体内成像表明,在磁共振(MR)引导下,Fe3O4-Au 纳米粒子在给药后 15 分钟提供了 34.61 倍的对比度增强。计算机断层扫描(CT)测量表明,Fe3O4-Au 纳米粒子的最高亨氏单位(HU)在注射后 30 分钟时为 174。在患有三种不同肝脏疾病的大鼠模型中进一步评估了 Fe3O4-Au 纳米粒子的体内性能。对于脂肪肝模型,在 MR(最高对比比 47.33)和 CT(从 19 HU 到 72 HU)引导下观察到几乎均匀的对比增强,没有出现局灶性结节或功能障碍。对于肝硬化和 HCC,在 Fe3O4-Au 注射后,肝脏实质中可以看到明显的增强,并且突出显示了病变。此外,病理、血液学和生化分析表明,急性和慢性毒性不存在,证实了我们的平台用于体内应用的生物相容性。总之,这些 Fe3O4-Au 纳米粒子作为多模态生物成像的候选物具有很大的潜力。
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