Gd(2)O(3)-mesoporous silica/gold nanoshells: A potential dual T(1)/T(2) 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 Gd(2)O(3)-mesoporous silica/gold core/shell NSs (Gd(2)O(3)-MS NSs) with NIR photothermal properties that also supply sufficient MRI contrast to be visualized at therapeutic doses (≥10(8) NSs per milliliter). The nanoparticles have r(1) relaxivities more than three times larger than those of conventional T(1) contrast agents, requiring less concentration of Gd(3+) to observe an equivalent signal enhancement in T(1)-weighted MR images. Furthermore, Gd(2)O(3)-MS NS nanoparticles have r(2) relaxivities comparable to those of existing T(2) contrast agents, observed in agarose phantoms. This highly unusual combination of simultaneous T(1) and T(2) contrast allows for MRI enhancement through different approaches. As a rudimentary example, we demonstrate T(1)/T(2) ratio MR images with sixfold contrast signal enhancement relative to its T(1) 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.