Trap-engineered inorganic phosphors act as an optical energy storage medium, thus enabling many applications ranging from persistent luminescence imaging to sono-optogenetics. Solid-state reactions are conventionally used to produce high-quality phosphors with large sizes, which prohibit their use in vivo. In contrast, phosphor nanoparticles produced at lower processing temperatures are limited in available host materials, crystal structures, and dopant types and concentrations. We borrow a strategy used by Nature to produce nonequilibrium nanostructures in biominerals such as the tooth enamel, to develop a general method for producing water-soluble solid-state phosphors with nanometer sizes. With this strategy, a wide range of solid-state phosphors can be processed to dissolve in water, yielding aqueous suspensions with distinct colors of afterglow. These solid-state nanophosphors enable them to act as systemically delivered light sources for transcranial afterglow imaging of fluorescent proteins in the brain with deep tissue penetration.