Design and Synthesis of Polymer-Functionalized NIR Fluorescent Dyes–Magnetic Nanoparticles for Bioimaging

The fluorescent probes having complete spectral separation between absorption and emission spectra (large Stokes shift) are highly useful for solar concentrators and bioimaging. In bioimaging application, NIR fluorescent dyes have a greater advantage in tissue penetration depth compared to visible-emitting organic dyes or inorganic quantum dots. Here we report the design, synthesis, and characterization of an amphiphilic polymer, poly(isobutylene-<i>alt</i>-maleic anhyride)-functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide (Fe₃O₄) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Our results demonstrate that the Stokes shift of unmodified dye can be tuned (from ∼106 to 208 nm) by the functionalization of the dye with polymer and MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The resulting uniform, small-sized (<i>ca</i>. 6 nm) NIR fluorescent dye–magnetic hybrid nanoparticles (NPs) exhibit a wider emissive range (800–1000 nm) and minimal cytotoxicity. Our preliminary studies demonstrate the potential utility of these NPs in bioimaging by means of direct labeling of cancerous HeLa cells <i>via</i> NIR fluorescence microscopy and good negative contrast enhancement in <i>T</i>₂-weighted MR imaging of a murine model