Paramagnetic silica-coated nangcrystals as an advanced MRI contrast agent

We present a robust and general method for embedding nanoparticles, such as quantum dots (QD) or colloidal gold (Au) nanocrystals, into a highly water-soluble thin silica shell doped with paramagnetic gadolinium (Gd ³⁺) ions without negatively impacting the optical properties of the QD or Au nanoparticle cores. The ultrathin silica shell has been covalently linked to Gd³⁺ ions chelator, tetraazacyclododecanetetraacetic acid (DOTA). The resulting complex has a diameter of 8 to 15 nm and is soluble in high ionic strength buffers at pH values ranging from approximately 4 to 11. For this system, nanoparticle concentrations exceed 50 μM, while most other nanoparticles might aggregate. In magnetic resonance imaging (MRI) experiments at clinical magnetic field strengths of 1.4 T (¹H resonance frequency of 60 MHz), the gadolinium-DOTA (Gd-DOTA) attached to SiO₂-coated QDs has a spin-lattice (T₁) particle relaxivity () and a spin-spin (T₂) particle relaxivity (r₂) of 1019 ±19 mM ^-1s^-1 and 2438 ±46 mM^-1 s^-1, respectively, for a 8-nm QD. The particle relaxivity has been correlated to the number of Gd³⁺ covalently linked to the silica shell. At 1.4 T, the Gd-DOTA ion relaxivities, r₁ and r₂, respectively, are 23 ±0.40 mM^-1s^-1 and 54 ±1.0 mM ^-1s^-1. The sensitivity of our probes is in the 100-nM range for 8-10 nm particles and reaches 10 nM for particles approximately 15 nm in diameter. Preliminary dynamic contrast enhancement MRI experiments in mice revealed that silica-coated MRI probes are cleared from the renal system into the bladder with no observable affects on the health of the animal. This current approach may offer numerous advantages over other similar approaches,12 including greater relaxivity and greater simplicity for the synthesis process of dual modality contrast agents that allow both MRI and optical detection as well as applicability to other nanoparticles.