Efficient control over drug release is critical to increasing drug efficacy and avoiding side effects. An ideal drug delivery system would deliver drugs in the right amount, at the right location and at the right time noninvasively. This can be achieved using light-triggered delivery: light is noninvasive, spatially precise and safe if appropriate wavelengths are chosen. However, the use of light-controlled delivery systems has been limited to areas that are not too deep inside the body because ultraviolet (UV) or visible (Vis) light, the typical wavelengths used for photoreactions, have limited penetration and are toxic to biological tissues. The advent of upconverting nanoparticles (UCNPs) has made it possible to overcome this crucial challenge. UCNPs can convert near-infrared (NIR) radiation, which can penetrate deeper inside the body, to shorter wavelength NIR, Vis and UV radiation. UCNPs have been used as bright, in situ sources of light for on-demand drug release and bioimaging applications. These remote-controlled, NIR-triggered drug delivery systems are especially attractive in applications where a drug is required at a specific location and time such as in anesthetics, postwound healing, cardiothoracic surgery and cancer treatment. In this Perspective, we discuss recent progress and challenges as well as propose potential solutions and future directions, especially with regard to their translation to the clinic.

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.

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A facile one-pot Stöber route is used to synthesize high-quality Ag, AgBr-silica-resorcinol formaldehyde polymer core-shell-shell nanospheres. The obtained core-shell-shell templates can be converted to Ag@carbon yolk-shell nanostructures with tunable dimensions.