title: Improving the MR Imaging Sensitivity of Upconversion Nanoparticles by an Internal and External Incorporation of the Gd(3+) Strategy for in Vivo Tumor-Targeted Imaging.
abstract: Gd(3+)-ion-doped upconversion nanoparticles (UCNPs), integrating the advantages of upconversion luminescence and magnetic resonance imaging (MRI) modalities, are capturing increasing attention because they are promising to improve the accuracy of diagnosis. The embedded Gd(3+) ions in UCNPs, however, have an indistinct MRI enhancement owing to the inefficient exchange of magnetic fields with the surrounding water protons. In this study, a novel approach is developed to improve the MR imaging sensitivity of Gd(3+)-ion-doped UCNPs. Bovine serum albumin (BSA) bundled with DTPA-Gd(3+) (DTPA(Gd)) is synthesized both as the MR imaging sensitivity synergist and phase-transfer ligand for the surface engineering of UCNPs. The external Gd(3+) ion attachment strategy is found to significant improve the MR imaging sensitivity of Gd(3+)-ion-doped UCNPs. The relaxivity analysis shows that UCNPs@BSA·DTPA(Gd) exhibit higher relaxivity values than do UCNPs@BSA without DTPA(Gd) moieties. Another relaxivity study discloses a striking message that the relaxivity value does not always reflect the realistic MRI enhancement capability. The high concentration of Gd(3+)-ion-containing UCNPs with further surface-engineered BSA·DTPA(Gd) (denoted as UCNPs-H@BSA·DTPA(Gd)) exhibits a more pronounced MRI enhancement capability compared to the other two counterparts [UCNPs-N@BSA·DTPA(Gd) and UCNPs-L@BSA·DTPA(Gd) (-N and -L are denoted as zero and low concentrations of Gd(3+) ion doping, respectively)], even though it holds the lowest r1 of 1.56 s(-1) per mmol L(-1) of Gd(3+). The physicochemical properties of UCNPs are essentially maintained after BSA·DTPA(Gd) surface decoration with good colloidal stability, in addition to improving the MR imaging sensitivity. In vivo T1-weighted MRI shows potent tumor-enhanced MRI with UCNPs-H@BSA·DTPA(Gd). An in vivo biodistribution study indicates that it is gradually excreted from the body via hepatobiliary and renal processing with no obvious toxicity. It could therefore be concluded, with improved MR imaging sensitivity by an internal and external incorporation of Gd(3+) strategy, that UCNPs-H@BSA·DTPA(Gd) presents great potential as an alternative in tumor-targeted MR imaging.
authors.forename: Hongli
authors.initials: H
authors.lastname: Du
authors.affiliation: Shanghai Skin Disease Hospital, The Institute for Photomedicine, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine , Shanghai 200443, China.
authors.forename: Jiani
authors.initials: J
authors.lastname: Yu
authors.forename: Dongcai
authors.initials: D
authors.lastname: Guo
authors.affiliation: School of Materials Science and Engineering, School of Life Science, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University , Tianjin 300072, China.
authors.forename: Weitao
authors.initials: W
authors.lastname: Yang
authors.affiliation: Shanghai Skin Disease Hospital, The Institute for Photomedicine, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine , Shanghai 200443, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Skin Disease Hospital, The Institute for Photomedicine, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine , Shanghai 200443, China.
authors.forename: Bingbo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002417:Cattle; D005682:Gadolinium / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000502:physiology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009369:Neoplasms / Q000000981:diagnostic imaging*; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D005682:Gadolinium