We have recently introduced the use of persistent luminescence nanoparticles, or long-lasting phosphors, for in vivo bioimaging applications in living animals. Red long-lasting phosphors possess an emission located in the tissue transparency window, between 600 and 900nm, allowing their use for in vivo imaging. Thanks to their optical properties, such nanoparticles can be excited before their systemic injection, allowing highly sensitive detection without any autofluorescence. This article reviews our recent work describing the influence of crystal size and surface state on the biodistribution of persistent luminescence nanoparticles after intravenous injection in living animal. Moreover, additional results from this collaboration show that a proper understanding of the fundamental mechanism associated with persistent luminescence in these silicate-based structures constitutes a major help to improve the optical properties of PLNP, resulting in a longer observation of the nanoprobes in vivo. Such promising results offer interesting perspectives for the development of persistent luminescence nanophosphors intended for long-term applications in living animals.