Engineered lanthanide-doped upconversion nanoparticles for biosensing and bioimaging application

Various fluctuations of intracellular ions, biomolecules, and other conditions in the physiological environment play crucial roles in fundamental biological processes. These factors are of great importance for analysis in biomedical detection. Nevertheless, developments of the simple, rapid, and accurate proof for specific detection still encounter major challenges. Upconversion nanoparticles (UCNPs), which could absorb multiple low-energy near-infrared light (NIR) photon excitation and emits high-energy photons caused by anti-Stokes shift, show unique upconversion luminescence (UCL) properties, for example, sharp emission band, high physicochemical stability like near-zero photobleaching, photo blinking in biological tissues, and long luminescence lifetime. Furthermore, the NIR used for the light source to excite UCNPs enable lower photo-damage effect and deeper penetration of tissue, and in the meantime, it can avoid the auto-fluorescence and light scattering from biological tissue interference. Thus, the lanthanide-doped UCNP-based functional platform with controlled structure, crystalline phase, size, and multicolor emission has become an appropriate nanomaterial for bioapplications such as biosensing, bioimaging, drug release, and therapies. In this review, the recent progress about synthesis and biomedical applications of UCNPs related to sensing and bioimaging is summarized. Firstly, the different luminescence mechanisms of the upconversion process are presented. Secondly, four of the most common methods for synthesizing UCNPs are compared as well as the advantages and disadvantages of these synthetic routes. Meanwhile, the surface modification of lanthanide-doped UCNPs was introduced to pave the way for their biochemistry applications. Next, this review detailed the biological applications of lanthanide-doped UCNPs, particularly in bioimaging, including UCL and multi-modal imaging and biosensing (monitoring intracellular ions and biomolecules). Finally, the challenges and future perspectives in materials science and biomedical fields of UCNPs are concluded: the low quantum yield of the upconversion process should be considered when they are executed as imaging contrast agents. And the biosafety of lanthanide-doped UCNPs needs to be evaluated.