A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window

Abstract

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 β-NaHoF4 core plus a β-NaGdF4:Yb , Tm 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 μs, due to the transition H → H of Tm . Proton nuclear magnetic relaxation dispersion ( H-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 T -weighted contrast agent below 1.5 T, a T /T dual-weighted contrast agent at 3 T, and as highly efficient T -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 μg mL .

High‐Field MRI Contrast Agents and their Synergy with Optical Imaging: the Evolution from Single Molecule Probes towards Nano‐architectures

“…To improve accuracy, the development of T 1 / T 2 dual‐weighted MRI using a single system can overcome some problems associated with image overlaying resulting from the reloading of samples and spatial/time resolution of multiple systems. Incorporating Fe 3 O 4 NPs as the T 2 relaxation agent with MnO or Gd 3+ as the T 1 agent are reported as T 1 / T 2 dual‐weighted MRI CAs . Lee et al.…”

“…However, these examples only exhibited T 1 / T 2 dual‐weighted MRI contrast enhancement at clinical fields. Very recently, the authors of this review developed a unique multimodal, magnetic resonance imaging/optical imaging (MRI/OI) contrast agent, based on core–shell nanoparticles composed of a β‐NaHoF 4 core covered in a β‐NaGdF 4 :Yb 3+ , Tm 3+ shell . When excited in the biological window using a 980 nm laser, the contrast agent (CA) shows intense and relatively long lived emission at 802 nm.…”

“… Variation in r 2 / r 1 values with respect to magnetic field (B 0 ); Reproduced with authors rights from Ref. The Royal Society of Chemistry …”

“…Incorporating Fe 3 O 4 NPs as the T 2 relaxation agent with MnO or Gd 3 + as the T 1 agenta re reported as T 1 /T 2 dual-weighted MRI CAs. [61,72] [70] Recently,Y ie tal. reportedt hat by doping Ln 3 + (Ln 3 + = Dy 3 + , Er 3 + or Yb 3 + )i nto aB aGdF 5 host, the T 1 /T 2 relaxivities of NPs can be tuned.…”

“…Very recently,t he authors of this review devel-oped au nique multimodal, magneticr esonance imaging/optical imaging (MRI/OI) contrast agent, based on core-shell nanoparticles composed of a b-NaHoF 4 core covered in a b-NaGd-F 4 :Yb 3 + ,T m 3 + shell. [72] When excited in the biological window using a9 80 nm laser,t he contrasta gent (CA) shows intense and relativelyl ong lived emission at 802 nm. Proton nuclear magnetic relaxation dispersion ( 1 H-NMRD) studies and magnetic resonance (MR) phantom imaging studies of thesen anoparticles, decorated with poly(acrylic acid) and folic acid on the surface, showedm agnetic field depended tuneable contrast properties.…”