Evaluation of Mesoporous Silica Nanoparticles as Carriers of Triarylmethyl Radical Spin Probes for EPR Oximetry.

In vivo measurement and mapping of oxygen levels within the tissues are crucial in understanding the physiopathological processes of numerous diseases, such as cancer, diabetes, or peripheral vascular diseases. Electron paramagnetic resonance (EPR) associated with biocompatible exogenous spin probes, such as Ox071 triarylmethyl (TAM) radical, is becoming the new gold standard for oxygen mapping in preclinical settings. However, these probes do not show tissue selectivity when injected systemically, and they are not cell permeable, reporting oxygen from the extracellular compartment only. Recently, Ox071-loaded mesoporous silica nanoparticles (MSNs) were proposed for intracellular tumor oxygen mapping in both in vitro and in vivo models. However, the EPR spectrum of the Ox071 spin probe is poorly sensitive to mobility due to the small anisotropy of its g-factor and the absence of hyperfine splitting, making it more difficult to study the mobility of the radical inside the MSNs or its location. Using 13C1 isotopologues of Ox071 and the deuterated Finland trityl (dFT) spin probes, which are highly sensitive to molecular tumbling, we showed that the loading of the probes inside homemade and commercial cationic MSNs drastically decreases their mobility while the high local concentration of the probe inside the MSNs leads to dipolar line width broadening (self-relaxation). This decrease in molecular tumbling and line broadening hampers the oxygen-sensing properties of Ox071 or dFT probes used for EPR oximetry when loaded into MSNs.