Remote activation of photoactivable therapeutic compounds by light provides a high spatial and temporal control for activating the therapeutic agent. However, photoactivable compounds are mostly responsive towards ultraviolet (UV) or visible light radiation that has poor tissue penetration depth besides being unsafe to the body in the case of UV light. Nanoparticles with energy upconversion hold potential in overcoming this limit by using safe and deeply penetrating near-infrared (NIR) light. These upconversion nanoparticles (UCNs) act as versatile nanotransducers as they convert NIR light to light of shorter wavelengths that can be tuned to the NIR, visible or UV colors to suit different activation wavelengths. Their highly unusual optical properties to fluoresce with near-zero photobleaching, photoblinking and background autofluorescence are unique and an added benefit when used simultaneously as optional imaging agents. This article reviews recent advancements in the use of UCNs for photoactivation of therapeutic agents. Specifically, we discuss the use of these UCNs for activation of light-sensitive/photocaged molecules or photosensitizers for photocontrolled-delivery and photodynamic therapy.
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