Gd₂O₃-mesoporous silica/gold nanoshells: A potential dual T₁/T₂ contrast agent for MRI-guided localized near-IR photothermal therapy

A promising clinical trial utilizing gold-silica core-shell nanostructures coated with polyethylene glycol (PEG) has been reported for near-infrared (NIR) photothermal therapy (PTT) of prostate cancer. The next critical step for PTT is the visualization of therapeutically relevant nanoshell (NS) concentrations at the tumor site. Here we report the synthesis of PEGylated Gd₂O₃-mesoporous silica/gold core/shell NSs (Gd₂O₃-MS NSs) with NIR photothermal properties that also supply sufficient MRI contrast to be visualized at therapeutic doses (≥10⁸ NSs per milliliter). The nanoparticles have r₁ relaxivities more than three times larger than those of conventional T₁ contrast agents, requiring less concentration of Gd³⁺ to observe an equivalent signal enhancement in T₁-weighted MR images. Furthermore, Gd₂O₃-MS NS nanoparticles have r₂ relaxivities comparable to those of existing T₂ contrast agents, observed in agarose phantoms. This highly unusual combination of simultaneous T₁ and T₂ contrast allows for MRI enhancement through different approaches. As a rudimentary example, we demonstrate T₁/T₂ ratio MR images with sixfold contrast signal enhancement relative to its T₁ MRI and induced temperature increases of 20 to 55 °C under clinical illumination conditions. These nanoparticles facilitate MRI-guided PTT while providing real-time temperature feedback through thermal MRI mapping.