Shaw Misa A, Poncelet Martin, Banerjee Derrick A, Sierros Konstantinos A, Driesschaert Benoit
Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, United States.
In Vivo Multifunctional Magnetic Resonance Center, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, West Virginia 26506, United States.
J Phys Chem B. 2025 Feb 13;129(6):1846-1854. doi: 10.1021/acs.jpcb.4c06480. Epub 2025 Jan 30.
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 and 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 C 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.
组织内氧水平的测量和绘图对于理解多种疾病（如癌症、糖尿病或外周血管疾病）的生理病理过程至关重要。与生物相容性外源性自旋探针（如Ox071三芳基甲基（TAM）自由基）相关的电子顺磁共振（EPR）正成为临床前环境中氧绘图的新金标准。然而，这些探针在全身注射时不显示组织选择性且不具有细胞渗透性，仅报告细胞外区室的氧。最近，有人提出将负载Ox071的介孔二氧化硅纳米颗粒（MSN）用于体内和体外模型中的细胞内肿瘤氧绘图。然而，由于Ox071自旋探针的g因子各向异性小且不存在超精细分裂，其EPR谱对迁移率的敏感性较差，这使得研究MSN内自由基的迁移率或其位置更加困难。使用对分子翻滚高度敏感的Ox071的C同位素类似物和氘代芬兰三苯甲基（dFT）自旋探针，我们表明，在自制的和商业阳离子MSN内负载探针会大幅降低其迁移率，而MSN内探针的高局部浓度会导致偶极线宽展宽（自弛豫）。当负载到MSN中时，分子翻滚的这种降低和线展宽会妨碍用于EPR血氧测定的Ox071或dFT探针的氧传感特性。
