Nanoparticle-based PARACEST agents: the quenching effect of silica nanoparticles on the CEST signal from surface-conjugated chelates


A. D. Sherry, Advanced Imaging Research Center, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.



Silica nanoparticles of average diameter 53 ± 3 nm were prepared using standard water-in-oil microemulsion methods. After conversion of the surface Si–OH groups to amino groups for further conjugation, the PARACEST agent, EuDOTA–(gly)4 was coupled to the amines via one or more side-chain carboxyl groups in an attempt to trap water molecules in the inner-sphere of the complex. Fluorescence and ICP analyses showed that ~1200 Eu3+ complexes were attached to each silica nanoparticle, leaving behind excess protonated amino groups. CEST spectra of the modified silica nanoparticles showed that attachment of the EuDOTA–(gly)4 to the surface of the nanoparticles did not result in a decrease in water exchange kinetics as anticipated, but rather resulted in a complete elimination of the normal Eu3+-bound water exchange peak and broadening of the bulk water signal. This observation was traced to catalysis of proton exchange from the Eu3+-bound water molecule by excess positively charged amino groups on the surface of the nanoparticles. Copyright © 2012 John Wiley & Sons, Ltd.