In Vivo Tracking of the Degradation of Mesoporous Silica through Zr-89 Radio-Labeled Core-Shell Nanoparticles

While mesoporous silica nanoparticles (MSNs) are extensively studied as high-potential drug delivery platforms, the successful clinical translation of these nanocarriers strongly depends on their biodistribution, biodegradation, and elimination patterns in vivo. Here, a novel method is reported to follow the in vivo degradation of MSNs by tracking a radioactive label embedded in the silica structure. Core-shell silica nanoparticles (NPs) with a dense core and a mesoporous shell are labeled with low quantities of the positron emitter Zr-89, either in the dense core or in the mesoporous shell. In vivo positron emission tomography imaging and ex vivo organ measurements reveal a remarkable difference in the Zr-89 biodistribution between the shell-labeled and the core-labeled NPs. Release of the radiotracer from shell-labeled NPs is used as a probe of the extent of silica dissolution, and a prompt release of the radioisotope is observed, with partial excretion already in the first 2 h post injection, and a slower accumulation in bones over time. On the other hand, when Zr-89 is embedded in the nanoparticle core, the biodistribution remains largely unchanged during the first 6 h. These findings indicate that MSNs have fast, hour-scale, degradation kinetics in vivo.