title: Multifunctional dendrimer-based nanoparticles for in vivo MR/CT dual-modal molecular imaging of breast cancer.
abstract: Development of dual-mode or multi-mode imaging contrast agents is important for accurate and self-confirmatory diagnosis of cancer. We report a new multifunctional, dendrimer-based gold nanoparticle (AuNP) as a dual-modality contrast agent for magnetic resonance (MR)/computed tomography (CT) imaging of breast cancer cells in vitro and in vivo. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers modified with gadolinium chelate (DOTA-NHS) and polyethylene glycol monomethyl ether were used as templates to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining dendrimer terminal amine groups; multifunctional dendrimer-entrapped AuNPs (Gd-Au DENPs) were formed. The formed Gd-Au DENPs were used for both in vitro and in vivo MR/CT imaging of human MCF-7 cancer cells. Both MR and CT images demonstrate that MCF-7 cells and the xenograft tumor model can be effectively imaged. The Gd-Au DENPs uptake, mainly in the cell cytoplasm, was confirmed by transmission electron microscopy. The cell cytotoxicity assay, cell morphology observation, and flow cytometry show that the developed Gd-Au DENPs have good biocompatibility in the given concentration range. Our results clearly suggest that the synthetic Gd-Au DENPs are amenable for dual-modality MR/CT imaging of breast cancer cells.
authors.affiliation: Department of Radiology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Kangan
authors.initials: K
authors.lastname: Li
authors.forename: Shihui
authors.initials: S
authors.lastname: Wen
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larson
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D013388:Succinimides / Q000737:chemistry; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D003287:Contrast Media; C502492:DOTA-NHS; D050091:Dendrimers; D013388:Succinimides
keywords: CT imaging; MR imaging; PAMAM dendrimers; PEGylation; breast cancer cells; gadolinium; gold nanoparticles