Decoupling Theranostics with Rare Earth Doped Nanoparticles

Theranostic nanoagents targeted for personalized medicine provide a unified platform for therapeutics and diagnostics. To be able to discretely control each individually, allows for safer, more precise, and truly multifunctional theranostics. Rare earth doped nanoparticles can be rationally tailored to best match this condition with the aid of core/shell engineering. In such nanoparticles, the light‐mediated theranostic approach is functionally decoupled—therapeutics or diagnostics are prompted on‐demand, by wavelength‐specific excitation. These decoupled rare earth nanoparticles (dNPs) operate entirely under near‐infrared (NIR) excitation, for minimized light interference with the target and extended tissue depth action. Under heating‐free 806 nm irradiation, dNPs behave solely as high‐contrast NIR‐to‐NIR optical markers and nanothermometers, visualizing and probing the area of interest without prompting the therapeutic effect beforehand. On the contrary, 980 nm NIR irradiation is upconverted by the dNPs to UV/visible light, which triggers secondary photochemical processes, e.g., generation of reactive oxygen species by photosensitizers coupled to the dNPs, causing damage to cancer cells. Additionally, integration of NIR nanothermometry helps to control the temperature in the vicinity of the dNPs avoiding possible overheating and quenching of upconversion (UC) emission, harnessed for photodynamic therapy. Overall, a new direction is outlined in the development of state‐of‐the‐art rare earth based theranostic nanoplatforms.