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 invitro and invivo 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 343.8s^-1mm^-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 invivo tumor targeting, near-infrared fluorescent and MR imaging by means of only using MHI-148 dye.