title: Targeted CT/MR dual mode imaging of tumors using multifunctional dendrimer-entrapped gold nanoparticles.
abstract: We report the synthesis and characterization of folic acid (FA)-modified multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) for targeted dual mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) modified with Gd(III) chelator, polyethylene glycol (PEG) monomethyl ether, and PEGylated FA were used as templates to entrap gold nanoparticles (AuNPs). Further chelation of Gd(III) ions and acetylation of the remaining dendrimer terminal amines led to the formation of multifunctional FA-targeted Au DENPs loaded with Gd(III) (Gd-Au DENPs-FA). The formed Gd-Au DENPs-FA probes were characterized via different techniques. We show that the Gd-Au DENPs-FA probes with an Au NP core size of 4.0 nm are water dispersible, stable under different pH and temperature conditions, and cytocompatible in the given concentration range. With the co-existence of AuNPs and Gd(III) ions within the single multifunctional particles, Gd-Au DENPs-FA displayed high X-ray attenuation intensity and reasonable r1 relaxivity. These properties of the particles enabled them to be used as dual mode nanoprobes for targeted CT/MR imaging of cancer cells in vitro and xenograft tumor model in vivo via FA receptor-mediated active targeting pathway. The strategy to design multifunctional nanoprobes using the versatile dendrimer nanotechnology may be extended to design various dual mode or multimode imaging agents for accurate diagnosis of different types of cancer.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Kangan
authors.initials: K
authors.lastname: Li
authors.forename: Shihui
authors.initials: S
authors.lastname: Wen
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Hongdong
authors.initials: H
authors.lastname: Cai
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; D016923:Cell Death; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry; D004195:Disease Models, Animal; D005492:Folic Acid / Q000378:metabolism; D006046:Gold / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D010316:Particle Size; D059629:Signal-To-Noise Ratio; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014965:X-Rays
chemical_list: D050091:Dendrimers; D006046:Gold; D005492:Folic Acid