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

Silica nanoparticles of average diameter 53±3nm 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.