Magnetic resonance imaging (MRI) is a powerful technique for obtaining tomographic images of biological targets in a noninvasive manner, with high spatial/temporal resolution, which makes it a vital component for diagnosing diseases such as cancer. Numerous studies have shown that the diagnostic value of MRI can be further improved by applying vectorized contrast agents, capable of delivering a high payload of para magnetic/superparamagnetic substances at the site of interest. However, because of the low intrinsic sensitivity of MRI compared to optical imaging, a relatively large local concentration of contrast agent is required to achieve the desired contrast enhancement. Looking exclusively at the sensitivity, optical imaging (OI) is more adequate for imaging as the local concentrations of contrast agents required are significantly lower. This issue of higher injection dose can be circumvented by adopting the technique of multimodal imaging, where different imaging modalities are combined within the frame of a single examination to obtain complementary information. Thus in the present study, a novel type of multimodal, magnetic resonance imaging/optical imaging (MRI/OI) contrast agent was developed, based on core–shell lanthanide fluoride nanoparticles composed of a b-NaHoF4 core plus a b-NaGdF4:Yb3+, Tm 3+ shell with an average size of ~24 nm. The biocompatibility of the particles was ensured by a surface modification with poly acrylic acid (PAA) and further functionalization with an affinity ligand, folic acid (FA). When excited using 980 nm near infrared (NIR) radiation, the contrast agent (CA) shows intense emission at 802 nm with lifetime of 791+/_3 ms, due to the transition 3H4!3H6 of Tm3+. Proton nuclear magnetic relaxation dispersion (1H-NMRD) studies and magnetic resonance (MR) phantom imaging showed that the newly synthesized nanoparticles, decorated with poly(acrylic acid) and folic acid on the surface (NP-PAA-FA), can act mainly as a T1weighted contrast agent below 1.5 T, a T1/T2 dual-weighted contrast agent at 3 T, and as highly efficient T2-weighted contrast agent at ultrahigh fields. In addition, NP-PAA-FA showed very low cytotoxicity and no detectable cellular damage up to a dose of 500 mgmL-1.
