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    Magnetic/Upconversion Fluorescent NaGdF4:Yb,Er Nanoparticle-Based Dual-Modal Molecular Probes for Imaging Tiny Tumors in Vivo
http://www.gaomingyuan.com  Thursday, August 01, 2013  17:00
     Magnetic materials, as the core material of a new type of magnetic resonance contrast agent, have been playing important role in early detection and treatment of diseases, especially for cancer. Following on from our previous investigations on Fe3O4-based MRI contrast agent and tumor-specific molecular probes, and NaGdF4 nanoparticle-based MRI probes to detect intraperitoneal tumor in vivo, We developed a dual-modality molecular probes to detect tiny tumor based on NaGdF4:Yb,Er nanoparticle. Differently sized NaGdF4:Yb,Er nanocrystals with narrow particle size distributions were synthesized by a high temperature approach. Upon ligand exchange, the as-prepared hydrophobic NaGdF4:Yb,Er nanocrystals were transferred into water by using asymmetric PEGs simultaneously bearing phosphate and maleimide groups. Further investigations demonstrated that the water-soluble NaGdF4:Yb,Er nanocrystals, coated by PEG bearing two phosphate groups on the same side, exhibit not only excellent colloidal stability in water and PBS buffer, but also pleasant upconversion fluorescence. Through “click” reaction between the maleimide residue on particle surface and thiol group from the partly reduced anti-EGFR monoclonal antibody (mAb), NaGdF4:Yb,Er-PEG-mAb nanoprobes were constructed. Then a series of in vivo experiments were then carried out for detecting intraperitoneal and subcutaneous tumor xenografts in nude mice by using magnetic resonance (MR) imaging and optical imaging technique. The results revealed that the probes could work well in dual–modal tumor–specific targeted imaging and succeeding in detecting tumor smaller than 2 mm. Furthermore, we evaluated the size-dependent pharmacokinetic behavior of NaGdF4 nanoparticles, including biodistribution, blood half time, and elimination pathway. The results have been accepted by ACS Nano recently.
     This work is a collaborated research by three groups with different research disciplines, including Prof. Mingyuan Gao’s group from Institute of Chemistry, CAS, Prof. Hao Lei’s group from Wuhan Institute of Physics & Mathematics, CAS, and Prof. Lin Shen’s group from School of Oncology, Peking University. Prof. Gao devoted a lot of his time and energy on conceiving the research, providing guidance, discussing the data, revising and improving the manuscript. Thanks to his patient guidance, and my abilities on research and cooperation have been greatly improved.
                                                                                                                                                                                                          Chunyan Liu et al.