Tuned Manganese-Impregnated Mesoporous Silica Nanoparticles as a pH-Responsive Dual Imaging Probe

The limitations of individual imaging modalities have led to significant interest in hybrid imaging methods that combine the advantages of multiple techniques. The development of diverse dual imaging agents, which offer the exceptional sensitivity of single-photon emission computed tomography (SPECT) and the high spatial resolution of magnetic resonance imaging (MRI), has been addressing the demand for more advanced diagnostic pharmaceuticals. In this study, ^99mTc-labeled manganese oxide-loaded mesoporous silica nanoparticles (MSNs), conjugated with folic acid as the targeting moiety and the chelating agent H₂pentapa-en-NH₂ (^99mTc-MnO_<i>x</i>-MSN-FA-pa), were developed for targeted SPECT-MRI dual imaging. The toxicity of the nanoparticles was confirmed through an MTT assay, showing >90% viability in HEK-293 and MDA-MB-231 cells at concentrations up to 200 μg/mL, indicating nonsignificant toxicity. Cellular uptake studies showed that folic acid functionalization effectively accentuated tumor-specific intracellular uptake of nanoparticles in MDA-MB-231 cells through folate receptor-mediated endocytosis. Additionally, the radiolabeling yield of ^99mTc-MnO_<i>x</i>-MSN-FA-pa was found to be 99.6 ± 0.8% (<i>n</i> = 3), and the pH-responsive release of paramagnetic manganese ions increased the <i>r</i>₁ relaxivity of the nanoprobe to 11.37 mM^-1 s^-1. In vivo SPECT imaging demonstrated rapid tracer accumulation in MDA-MB-231 xenografts, with a tumor-to-muscle ratio of 6.01 ± 0.51 at 2 h, and minimal uptake in nontargeted organs. In vivo MRI studies indicated the strongest tumor contrast at 2 h postinjection. Given its desirable contrast enhancement in T₁ MRI and SPECT imaging, along with low toxicity, MnO_<i>x</i>-MSN-FA-pa shows potential as an effective multifunctional nanoprobe for precise tumor imaging.