Bimodal over–1000 nm near–infrared (OTN–NIR) fluorescence and magnetic resonance (MR) imaging can provide a notable platform for revealing multidimensional information with high sensitivity and spatial resolution, together with an effective deep tissue penetration. The combination is facilitated by developing a bimodal OTN-NIR/MRI imaging probe.

Most bimodal OTN-NIR/MRI imaging probes are derived from rare-earth-doped ceramic nanoparticles (RED-CNPs). However, RED-CNPs often require a diameter larger than 100 nm to emit detectable fluorescence. The large diameter structures tend to induce reticuloendothelial system (RES) recognition and be captured in the liver, thus reducing the imaging efficacy. Moreover, inorganic structures raise concerns about toxicity when applied in humans. Therefore, the probes deriving from organic compounds are preferable.

New OTN-NIR/MRI imaging probes from biodegradable polymeric micelles have been reported recently. The structures had relatively small diameters (less than 50 nm) and were composed of Gd-DOTA, an MRI contrast agent, conjugated on poly(lactic–co–glycolic acid)–block–poly(ethylene glycol) copolymer (PLGA–PEG) micelles encapsulated IR-1061 dye. The architecture design shows a substantial role in optimizing the properties and behaviors of the probes. Specifically, the fluorescence is primarily governed by the affinity between the dye and the hydrophobic core. If affinity is mismatched, the dye is propelled out of the center and rapidly quenched by nearby water molecules.

Meanwhile, the introduced Gd-DOTA remarkably contributes to the MRI contrast enhancement, the fluorescence properties, and the biological responsiveness of the probe. When Gd-DOTA is located on the micellar surface, the structure is strongly interfered with by external molecules such as water of plasma proteins, resulting in fluorescence quenching. The impingement is only improved by reducing the introduction ratios. On the other hand, when Gd-DOTA is located on the core border, Gd-DOTAs form a cross-coordinated barrier across the core boundary against any intrusion from external environments and preserve the fluorescence together with MRI contrast enhancement. Herein, we review the development of the OTN-NIR/MR bimodal imaging probes from polymeric micelles and the influence of their architectures on the imaging.