title: Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.
authors.affiliation: Shanghai Institute of Medical Imaging, Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Shanghai Institute of Medical Imaging, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Shuohui
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Medical Imaging, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Jinguo
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.affiliation: Shanghai Institute of Medical Imaging, Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang