title: Ultrastable polyethyleneimine-stabilized gold nanoparticles modified with polyethylene glycol for blood pool, lymph node and tumor CT imaging.
abstract: Development of new long-circulating contrast agents for computed tomography (CT) imaging of different biological systems still remains a great challenge. Here, we report the design and synthesis of branched polyethyleneimine (PEI)-stabilized gold nanoparticles (Au PSNPs) modified with polyethylene glycol (PEG) for blood pool, lymph node, and tumor CT imaging. In this study, thiolated PEI was first synthesized and used as a stabilizing agent to form AuNPs. The formed Au PSNPs were then grafted with PEG monomethyl ether via PEI amine-enabled conjugation chemistry, followed by acetylation of the remaining PEI surface amines. The formed PEGylated Au PSNPs were characterized via different methods. We show that the PEGylated Au PSNPs with an Au core size of 5.1 nm have a relatively long half-decay time (7.8 h), and display a better X-ray attenuation property than conventionally used iodine-based CT contrast agents (e.g., Omnipaque), and are hemocompatible and cytocompatible in a given concentration range. These properties of the Au PSNPs afford their uses as a contrast agent for effective CT imaging of the blood pool and major organs of rats, lymph node of rabbits, and the xenografted tumor model of mice. Importantly, the PEGylated Au PSNPs could be excreted out of the body with time and also showed excellent in vivo stability. These findings suggest that the formed PEGylated Au PSNPs may be used as a promising contrast agent for CT imaging of different biological systems.
authors.affiliation: Department of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. sawboneszhao@163.com.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn.
authors.forename: Shihui
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. zhaojinhua1963@126.com.
authors.forename: Lingzhou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Du
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. zhaojinhua1963@126.com.
authors.forename: Changcun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. sawboneszhao@163.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. sawboneszhao@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. sawboneszhao@163.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Cardiac Surgery, University of Rostock, 18055, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. zhaojinhua1963@126.com.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn and State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China. sawboneszhao@163.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D003102:Colloids / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D007455:Iodine / Q000737:chemistry; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D036103:Nanotechnology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014057:Tomography, X-Ray Computed; D014965:X-Rays
chemical_list: D001672:Biocompatible Materials; D003102:Colloids; D003287:Contrast Media; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D006046:Gold; D011094:Polyethyleneimine; D007455:Iodine