title: Synthesis and application of strawberry-like Fe3O4-Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: Institute of Materials Engineering, National Laboratory of Solid State Microstructure, College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Radiology, Drum Tower Hospital, School of Medicine, Nanjing University, Jiangsu, 210093, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: Institute of Materials Engineering, National Laboratory of Solid State Microstructure, College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, PR China.
authors.forename: Chao C
authors.initials: CC
authors.lastname: Pan
authors.affiliation: Department of Radiology, Drum Tower Hospital, School of Medicine, Nanjing University, Jiangsu, 210093, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Radiology, Drum Tower Hospital, School of Medicine, Nanjing University, Jiangsu, 210093, PR China.
authors.forename: Zheng Y
authors.initials: ZY
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Jiangsu, 210093, PR China. Electronic address: dingyin@nju.edu.cn.
authors.forename: Yin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Institute of Materials Engineering, National Laboratory of Solid State Microstructure, College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, PR China. Electronic address: allicinhonda@163.com.
authors.forename: Da
authors.initials: D
authors.lastname: Huo
authors.affiliation: Institute of Materials Engineering, National Laboratory of Solid State Microstructure, College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, PR China. Electronic address: hvyong@nju.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D018450:Disease Progression; D005234:Fatty Liver / Q000175:diagnosis / Q000473:pathology; D052203:Ferrosoferric Oxide / Q000138:chemical synthesis* / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008107:Liver Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D064847:Multimodal Imaging; D009928:Organ Specificity; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D006046:Gold; D052203:Ferrosoferric Oxide
keywords: Computed tomography; Gold nanoparticle; Hepatocellular carcinoma; Iron oxide; Liver cirrhosis; Magnetic resonance imaging