Size-controlled bimodal in vivo nanoprobes as near-infrared phosphors and positive contrast agents for magnetic resonance imaging

Rare-earth-doped nanoparticles (NPs), such as NaGdF(4) nanocrystals doped with light-emitting rare earth ions, are promising bimodal probes that allow the integration of over 1000 nm near-infrared (OTN-NIR; NIR-II/III) fluorescence imaging and magnetic resonance imaging (MRI) of live bodies. A precise control of the particle size is the key factor for achieving a high signal-to-noise ratio in both NIR fluorescence and MR images and for regulating their function in the body. In this study, size-controlled NaGdF(4):Yb(3+), Er(3+) NPs prepared by stepwise crystal growth were used for in vivo bimodal imaging. Hexagonal NaGdF(4):Yb(3+),Er(3+) NPs coated with poly(ethylene glycol)-poly(acrylic acid) block copolymer, with hydrodynamic diameters of 15 and 45 nm, were prepared and evaluated as bimodal NPs for OTN-NIR fluorescence imaging and MRI. Their longitudinal (T(1)) and transverse (T(2)) relaxation rates at the static magnetic field strength of 1.0 T, as well as their cytotoxicity towards NIH3T3 cell lines, were evaluated and compared to study the effect of size. Using these particles, blood vessel visualization was achieved by MRI, with the highest relaxometric ratio (r(1)/r(2)) of 0.79 reported to date for NaGdF(4)-based nanoprobes (r(1) = 19.78 mM(−1) s(−1)), and by OTN-NIR fluorescence imaging. The results clearly demonstrate the potential of the size-controlled PEG-modified NaGdF(4):Yb(3+),Er(3+) NPs as powerful ‘positive’ T(1)-weight contrast MRI agents and OTN-NIR fluorophores.