# Evaluation of Mesoporous Silica Nanoparticles as Carrier of Triarylmethyl Radical Spin Probes for EPR Oximetry

## TL;DR

This paper evaluates how mesoporous silica nanoparticles affect the performance of spin probes used for measuring oxygen levels in tissues.

## Contribution

The study reveals that loading spin probes into nanoparticles reduces their mobility and alters EPR signals, impacting oxygen sensing.

## Key findings

- Loading Ox071 and dFT spin probes into MSNs reduces their molecular tumbling.
- High probe concentration in MSNs causes linewidth broadening due to self-relaxation.
- These changes impair the oxygen-sensing capabilities of the spin probes in EPR oximetry.

## Abstract

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 pre-clinical settings. However, these probes don’t 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 lead to dipolar linewidth broadening (self-relaxation). This decrease in molecular tumbling and line broadening hamper the oxygen-sensing properties of Ox071 or dFT probes used for EPR oximetry when loaded into MSNs.