title: Core-shell hybrid upconversion nanoparticles carrying stable nitroxide radicals as potential multifunctional nanoprobes for upconversion luminescence and magnetic resonance dual-modality imaging.
abstract: Nitroxide radicals, such as 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) and its derivatives, have recently been used as contrast agents for magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI). However, their rapid one-electron bioreduction to diamagnetic N-hydroxy species when administered intravenously has limited their use in in vivo applications. In this article, a new approach of silica coating for carrying stable radicals was proposed. A 4-carboxyl-TEMPO nitroxide radical was covalently linked with 3-aminopropyl-trimethoxysilane to produce a silanizing TEMPO radical. Utilizing a facile reaction based on the copolymerization of silanizing TEMPO radicals with tetraethyl orthosilicate in reverse microemulsion, a TEMPO radicals doped SiO2 nanostructure was synthesized and coated on the surface of NaYF4:Yb,Er/NaYF4 upconversion nanoparticles (UCNPs) to generate a novel multifunctional nanoprobe, PEGylated UCNP@TEMPO@SiO2 for upconversion luminescence (UCL) and magnetic resonance dual-modality imaging. The electron spin resonance (ESR) signals generated by the TEMPO@SiO2 show an enhanced reduction resistance property for a period of time of up to 1 h, even in the presence of 5 mM ascorbic acid. The longitudinal relaxivity of PEGylated UCNPs@TEMPO@SiO2 nanocomposites is about 10 times stronger than that for free TEMPO radicals. The core-shell NaYF4:Yb,Er/NaYF4 UCNPs synthesized by this modified user-friendly one-pot solvothermal strategy show a significant enhancement of UCL emission of up to 60 times more than the core NaYF4:Yb,Er. Furthermore, the PEGylated UCNP@TEMPO@SiO2 nanocomposites were further used as multifunctional nanoprobes to explore their performance in the UCL imaging of living cells and T1-weighted MRI in vitro and in vivo.
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China. xqguo@xmu.edu.cn renlei@xmu.edu.cn.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Ren
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Guo
mesh_terms: D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis; D003287:Contrast Media / Q000138:chemical synthesis; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004058:Diffusion; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D058608:Nanopores / Q000648:ultrastructure; D009589:Nitrogen Oxides / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D013347:Subcellular Fractions / Q000473:pathology*
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D003497:Cyclic N-Oxides; D053769:Nanocapsules; D009589:Nitrogen Oxides; D012822:Silicon Dioxide; C039900:nitroxyl; C003959:TEMPO