Water-Soluble Bimodal\nMagnetic-Fluorescent Radical\nDendrimers as Potential MRI-FI Imaging Probes

Dual or multimodal imaging probes have become potent\ntools for\nenhancing detection sensitivity and accuracy in disease diagnosis.\nIn this context, we present a bimodal imaging dendrimer-based structure\nthat integrates magnetic and fluorescent imaging probes for potential\napplications in magnetic resonance imaging and fluorescence imaging.\nIt stands out as one of the rare examples where bimodal imaging probes\nuse organic radicals as the magnetic source, despite their tendency\nto entirely quench fluorophore fluorescence. Opting for organic radicals\nover metal-based contrast agents like gadolinium (Gd<sup>3+</sup>)-chelates\nis crucial to mitigate associated toxicity concerns. We utilized an\namino-terminated polyamide dendrimer containing a 1,8-naphthalimide\n(<b>Naft</b>) fluorescent group, amino acid derivatives as linkers\nto enhance water solubility, and TEMPO organic radicals as terminal\ngroups. The same dendrimer structure, featuring an equivalent number\nof branches but lacking the fluorophore group, was also functionalized\nwith amino acid and terminal radicals to serve as a reference. Remarkably,\nwe achieved a fully water-soluble dendrimer-based structure exhibiting\nboth magnetic and fluorescent properties simultaneously. The fluorescence\nof the <b>Naft</b> group in the final structure is somewhat\nquenched by the organic radicals, likely due to photoinduced electron\ntransfer with the nitroxyl radical acting as an electron acceptor,\nwhich has been supported by density functional theory calculations.\nMolecular dynamics simulations are employed to investigate how the\ndendrimers’ structure influences the electron paramagnetic\nresonance characteristics, relaxivity, and fluorescence. In summary,\ndespite the influence of the radicals–fluorophore interactions\non fluorescence, this bimodal dendrimer demonstrates significant fluorescent\nproperties and effective <i>r</i><sub>1</sub> relaxivity\nof 1.3 mM<sup>–1</sup> s<sup>–1</sup>. These properties\nhave proven effective in staining the live mesenchymal stem cells\nwithout affecting the cell nucleus.