title: Facile formation of dendrimer-stabilized gold nanoparticles modified with diatrizoic acid for enhanced computed tomography imaging applications.
abstract: We report a facile approach to forming dendrimer-stabilized gold nanoparticles (Au DSNPs) through the use of amine-terminated fifth-generation poly(amidoamine) (PAMAM) dendrimers modified by diatrizoic acid (G5.NH(2)-DTA) as stabilizers for enhanced computed tomography (CT) imaging applications. In this study, by simply mixing G5.NH(2)-DTA dendrimers with gold salt in aqueous solution at room temperature, dendrimer-entrapped gold nanoparticles (Au DENPs) with a mean core size of 2.5 nm were able to be spontaneously formed. Followed by an acetylation reaction to neutralize the dendrimer remaining terminal amines, Au DSNPs with a mean size of 6 nm were formed. The formed DTA-containing [(Au(0))(50)-G5.NHAc-DTA] DSNPs were characterized via different techniques. We show that the Au DSNPs are colloid stable in aqueous solution under different pH and temperature conditions. In vitro hemolytic assay, cytotoxicity assay, flow cytometry analysis, and cell morphology observation reveal that the formed Au DSNPs have good hemocompatibility and are non-cytotoxic at a concentration up to 3.0 μM. X-ray absorption coefficient measurements show that the DTA-containing Au DSNPs have enhanced attenuation intensity, much higher than that of [(Au(0))(50)-G5.NHAc] DENPs without DTA or Omnipaque at the same molar concentration of the active element (Au or iodine). The formed DTA-containing Au DSNPs can be used for CT imaging of cancer cells in vitro as well as for blood pool CT imaging of mice in vivo with significantly improved signal enhancement. With the two radiodense elements of Au and iodine incorporated within one particle, the formed DTA-containing Au DSNPs may be applicable for CT imaging of various biological systems with enhanced X-ray attenuation property and detection sensitivity.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Kangan
authors.initials: K
authors.lastname: Li
authors.forename: Xueyan
authors.initials: X
authors.lastname: Cao
authors.forename: Tingting
authors.initials: T
authors.lastname: Xiao
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Hou
authors.forename: Linfeng
authors.initials: L
authors.lastname: Zheng
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry*; D003973:Diatrizoate / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006046:Gold / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000000981:diagnostic imaging; D013696:Temperature; D014057:Tomography, X-Ray Computed
chemical_list: D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D003973:Diatrizoate; D006046:Gold