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Integrin α2β1 targeted GdVO4:Eu ultrathin nanosheet for multimodal PET/MR imaging

Hu, He, Li, Dan, Liu, Shuanglong, Wang, Mengzhe, Moats, Rex, Conti, Peter S., Li, Zibo
Biomaterials 2014 v.35 no.30 pp. 8649-8658
chelating agents, cytotoxicity, fluorescence, fluorescence microscopy, image analysis, integrins, ligands, magnetic resonance imaging, mice, nanosheets, polyacrylic acid, positron-emission tomography, prostatic neoplasms, radioactivity, therapeutics, tissues
Multifunctional nanoprobes open exciting possibilities for accurate diagnosis and therapy. In this research, we developed a ⁶⁴Cu-labeled GdVO4:4%Eu two-dimension (2D) tetragonal ultrathin nanosheets (NSs) that simultaneously possess radioactivity, fluorescence, and paramagnetic properties for multimodal imaging. The carboxyl-functionalized Eu³⁺-doped GdVO4 NSs were synthesized by a facile solvothermal reaction, followed by ligand exchange with polyacrylic acid (PAA). With ultrathin thickness of ∼5 nm and width of ∼150 nm, the carboxyl-functionalized NSs were further modified by DOTA chelator for ⁶⁴Cu labeling and Asp-Gly-Glu-Ala (DGEA) peptide for integrin α2β1 targeting. After initial evaluation of the cytotoxicity and targeting capability with PC-3 cells, the obtained multifunctional nanoprobes (⁶⁴Cu-DOTA-GdVO4:4%Eu-DGEA) were further explored for targeted positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) of PC-3 tumor (prostate cancer, high integrin α2β1 expression) in vivo. Based on the strong fluorescence of the NSs, the particle distribution in mouse tissues was also determined by fluorescent microscopy. In summary, GdVO4:4%Eu NS is a potential multimodal multiscale nanoprobe that could not only be used for in vivo imaging, but also be tracked in cellular scale and ex vivo due to its fluorescent property.