Tuned Manganese-Impregnated\nMesoporous Silica Nanoparticles\nas a pH-Responsive Dual Imaging Probe

The limitations of individual imaging\nmodalities have led to significant\ninterest in hybrid imaging methods that combine the advantages of\nmultiple techniques. The development of diverse dual imaging agents,\nwhich offer the exceptional sensitivity of single-photon emission\ncomputed tomography (SPECT) and the high spatial resolution of magnetic\nresonance imaging (MRI), has been addressing the demand for more advanced\ndiagnostic pharmaceuticals. In this study, <sup>99m</sup>Tc-labeled\nmanganese oxide-loaded mesoporous silica nanoparticles (MSNs), conjugated\nwith folic acid as the targeting moiety and the chelating agent H<sub>2</sub>pentapa-en-NH<sub>2</sub> (<sup>99m</sup>Tc-MnO<sub><i>x</i></sub>-MSN-FA-pa), were developed for targeted SPECT-MRI\ndual imaging. The toxicity of the nanoparticles was confirmed through\nan MTT assay, showing >90% viability in HEK-293 and MDA-MB-231\ncells\nat concentrations up to 200 μg/mL, indicating nonsignificant\ntoxicity. Cellular uptake studies showed that folic acid functionalization\neffectively accentuated tumor-specific intracellular uptake of nanoparticles\nin MDA-MB-231 cells through folate receptor-mediated endocytosis.\nAdditionally, the radiolabeling yield of <sup>99m</sup>Tc-MnO<sub><i>x</i></sub>-MSN-FA-pa was found to be 99.6 ± 0.8%\n(<i>n</i> = 3), and the pH-responsive release of paramagnetic\nmanganese ions increased the <i>r</i><sub>1</sub> relaxivity\nof the nanoprobe to 11.37 mM<sup>–1</sup> s<sup>–1</sup>. In vivo SPECT imaging demonstrated rapid tracer accumulation in\nMDA-MB-231 xenografts, with a tumor-to-muscle ratio of 6.01 ±\n0.51 at 2 h, and minimal uptake in nontargeted organs. In vivo MRI\nstudies indicated the strongest tumor contrast at 2 h postinjection.\nGiven its desirable contrast enhancement in T<sub>1</sub> MRI and\nSPECT imaging, along with low toxicity, MnO<sub><i>x</i></sub>-MSN-FA-pa shows potential as an effective multifunctional\nnanoprobe for precise tumor imaging.