Micelles have been extensively used in biomedicine as potential carriers of hydrophobic fluorescent dyes. Their small diameters can potentially enable them to evade recognition by the reticuloendothelial system, resulting in prolonged circulation. Nevertheless, their lack of stability in physiological environments limits the imaging utility of micelles. In particular, when a dye sensitive to water, such as IR-1061, is encapsulated in the micelle core, the destabilized structure leads to interactions between water and dye, degrading the fluorescence. In this study, we investigated a method to improve micelle stability utilizing the electrical effect of gadolinium (Gd3+ ) and tetraazacyclododecane tetraacetic acid (DOTA), introduced into the micelles. Three micellar structures, one containing a poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) block copolymer, and two other structures, including PLGA-b-PEG with DOTA or Gd-DOTA introduced at the boundary of PLGA and PEG, were prepared with IR-1061 in the core. Structures that contained DOTA at the border of the PLGA core and PEG shell exhibited much higher fluorescence intensity than probes without DOTA. With Gd3+ ions at the DOTA center, fluorescence stability was enhanced remarkably in physiological environments. Most interesting is the finding that fluorescence is enhanced with increased Gd-DOTA concentrations. In conclusion, we found that overall fluorescence and stability are improved by introducing Gd-DOTA at the boundary of the PLGA core and PEG shell. Improving micelle stability is crucial for further biomedical applications of micellar probes such as bimodal fluorescence and magnetic resonance imaging.
Keywords: Gd-DOTA; NIR-II; PLGA-PEG; fluorescence imaging; micelles.
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