Tumor targeting and MR imaging with lipophilic cyanine-mediated near-infrared responsive porous Gd silicate nanoparticles

We synthesize a NIR MHI-148 dye, a lipophilic heptamethine cyanine, with capability in tumor-targeting property to accumulate in the mitochondria of tumor. In the context of MHI-148 dye, we demonstrate effective tumor targeting and NIR fluorescence in vitro and in vivo for MHI-148 as compared to ICG. A series of porous Gd silicates related nanoparticles, i.e. Gd silicate, Gd silicate@mSiO2 (mSiO2: mesoporous silica shell), and Gd3+-chelated Gd silicate@mSiO2 (Gd3+-DOTA chelated on the mSiO2) are fabricated to demonstrate their magnetic resonance (MR) contrast imaging effects. Those Gd silicates related nanoparticles exhibit dual MR effect, expressing T1-brightened and T2-darkened effects, in lower magnetic field. In high magnetic field, an abnormal enhanced transverse relaxivity (r2) appears, showing an effective T2-lowering effect, possibly due to concentrated Gd amount and porous architecture. The r2 value increases 4-5 times as the field strength increased from 3T to 7T. The Gd3+-chelated Gd silicate@mSiO2 has given large r2 (T2-lowering effect) up to 343.8 s−1 mm−1, which is even larger than the reported magnetic Fe3O4 nanoparticles measured at the same field. Using a 9.4T animal micro MRI system we have seen effectively darken in signal for those porous Gd silicates related NPs, while no such phenomenon appears in commercial Gd-DOTA agent. The MHI-148 is then conjugated on the porous Gd silicate@mSiO2 nanoparticles for a new paradigm with three functionalities for in vivo tumor targeting, near-infrared fluorescent and MR imaging by means of only using MHI-148 dye.