title: Magnetic/upconversion fluorescent NaGdF4:Yb,Er nanoparticle-based dual-modal molecular probes for imaging tiny tumors in vivo.
abstract: Detection of early malignant tumors remains clinically difficult; developing ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual magnetic and optical properties associated with f-electrons, rare-earth elements are very suitable for creating functional materials potentially useful for tumor imaging. Nanometer-sized particles offer such a platform with which versatile unique properties of the rare-earth elements can be integrated. Yet the development of rare-earth nanoparticle-based tumor probes suitable for imaging tiny tumors in vivo remains difficult, which challenges not only the physical properties of the nanoparticles but also the rationality of the probe design. Here we report new approaches for size control synthesis of magnetic/upconversion fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the size and shape regulation mechanisms were investigated. By replacing the oleic acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size and upconversion fluorescence were obtained. Accordingly, a dual-modality molecular tumor probe was prepared, as a proof of concept, by covalently attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a "click" reaction. Systematic investigations on tumor detections, through magnetic resonance imaging and upconversion fluorescence imaging, were carried out to image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the excellent properties of the molecular probes, tumors smaller than 2 mm was successfully imaged in vivo. In addition, pharmacokinetic studies on differently sized particles were performed to disclose the particle size dependent biodistributions and elimination pathways.
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Bei Yi Jie 2, Zhong Guan Cun, Beijing 100190, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Gao
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zeng
authors.forename: Yi
authors.initials: Y
authors.lastname: Hou
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Yilin
authors.initials: Y
authors.lastname: Li
authors.forename: Ruirui
authors.initials: R
authors.lastname: Qiao
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.forename: Hao
authors.initials: H
authors.lastname: Lei
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yang
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Gao
mesh_terms: D000818:Animals; D002470:Cell Survival; D003952:Diagnostic Imaging; D004871:Erbium / Q000737:chemistry; D005243:Feces; D005456:Fluorescent Dyes / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D008024:Ligands; D008280:Magnetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D015335:Molecular Probes / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009374:Neoplasms, Experimental / Q000473:pathology; D009829:Oleic Acids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D015018:Ytterbium / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D015335:Molecular Probes; D009829:Oleic Acids; D005461:Fluorine; D011092:Polyethylene Glycols; D004871:Erbium; D012964:Sodium; D005682:Gadolinium; D015018:Ytterbium