The ultimate goal of in vivo imaging is to provide safe tools to probe the inside of a body in order to obtain pathological informations, monitor activities, examine disease progression or regression, track drug distribution, and evaluate drug efficacy. To reach such a goal, the development of contrast agent is highly required. Recent developments in nanotechnology have paved the way for dramatic changes in medical field for diagnosis of various diseases, their treatment, and their prevention. Nanotechnology is an interdisciplinary and multidisciplinary research field involving chemistry, physics, material science, biology, and medicine. Through the benefits achieved at the nanoscale such as controlled distribution, enhanced sensitivity, and multifunctional materials, these innovations are starting to change the landscape of modern medicine. Fluorescence imaging has become a dominant visualization method in biomedical research due to its high sensitivity, its high spatial resolution, its ease of use and very low cost. In vivo imaging of exogenous fluorescent probes that target diseased tissues has shown promising results in clinical settings, such as the early detection of breast cancer, the outlining of tumour margins during surgery and endoscopic diagnosis of cancer micrometastasis. However, the method is limited by tissue attenuation (scattering and absorption of the excitation or the emission light) and by tissue autofluorescence. To minimize tissue attenuation effects, researchers have concentrated on near infrared (NIR) fluorophores that are excited and emit in the spectral window between wavelengths of 650–950 nm. However, tissue autofluorescence still produces a substantial background signal in this spectral range that severely limits the quality of images, especially when very low concentrations of the fluorescent probe accumulate at the target site. Contrary to conventional commercial optical probes, such as NIR molecules or QDs that require continuous excitation to fluoresce, persistent luminescence material can stored and slowly release light for minutes to hours. This property is of particular interest for in vivo bioimaging since it allows to obtain images with a complete avoidance of the autofluorescence signal coming from endogeneous chromophors. The first generation of persistent luminescence nanoparticles (PLNP) discovered in 2006 validated the faisability of this promising technology. However it was limited, because the nanoprobe could only be excited before animal injection, limiting the observation time to only few hours. However, in 2013, a breakthrough was achieved by partners 1 & 2 when discovering an essential property of the second generation of PLNP, based on zinc gallate doped with 0.25% of Cr3+ (ZGO), whose persistent luminescence can be activated, whenever needed in vivo through living tissues, using highly penetrating low energy photons [CNRS patent, WOEP2013/051727, WO2013/113721, 08/08/2013; Nature Materials 2014, 13, 418-426]. This property demonstrated not only a real progress for bioimaging applications compared to the previous generation, but also compared to commercial NIR probes. However, this newly discovered nanoprobe suffers from a number of deficiencies, among them: 1) its relatively large size: the current synthesis process gives access to 80 nm (HD) in too small quantity, 2) possibility to adapt the emission wavelengths into the biological window (Yb Ni, Cr in spinel and garnet hosts) and to try different excitation processes, 3) no informations are available both on the fate of PLNP after intravenous injection and on their toxicological impact. For these reasons, the consortium gathers researchers who will bring all their expertise to answer/improve these different points and to consolidate the emergence of these promising nanoprobes in the field of advanced materials for innovative nanomedicine.