Lanthanide-doped upconverting nanoparticles (UCNPs) have recently attracted enormous attention in the field of biological imaging owing to their unique optical properties: (1) efficient upconversion photoluminescence, which is intense enough to be detected at the single-particle level with a (nonscanning) wide-field microscope setup equipped with a continuous wave (CW) near-infrared (NIR) laser (980 nm), and (2) resistance to photoblinking and photobleaching. Moreover, the use of NIR excitation minimizes adverse photoinduced effects such as cellular photodamage and the autofluorescence background. Finally, the cytotoxicity of UCNPs is much lower than that of other nanoparticle systems. All these advantages can be exploited simultaneously without any conflicts, which enables the establishment of a novel UCNP-based platform for wide-field two-photon microscopy. UCNPs are also useful for multimodal in vivo imaging because simple variations in the composition of the lattice atoms and dopant ions integrated into the particles can be easily implemented, yielding various distinct biomedical activities relevant to magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). These multiple functions embedded in a single type of UCNPs play a crucial role in precise disease diagnosis. The application of UCNPs is extended to therapeutic fields such as photodynamic and photothermal cancer therapies through advanced surface conjugation schemes.

Inorganic nanoparticle-based biomedical imaging probes have been studied extensively as a potential alternative to conventional molecular imaging probes. Not only can they provide better imaging performance but they can also offer greater versatility of multimodal, stimuli-responsive, and targeted imaging. However, inorganic nanoparticle-based probes are still far from practical use in clinics due to safety concerns and less-optimized efficiency. In this context, it would be valuable to look over the underlying issues. This outlook highlights the recent advances in the development of inorganic nanoparticle-based probes for MRI, CT, and anti-Stokes shift-based optical imaging. Various issues and possibilities regarding the construction of imaging probes are discussed, and future research directions are suggested.