Gadolinium-based ultra-small rigid platform nanoparticles (USRPs) as a theranostic agent for the imaging and treatment of lung cancer administered via nebulization. (a) Schematic representation of the USRP system and its components, which allow for ultrashort echo time magnetic resonance and fluorescence imaging alongside radiotherapy. (b) Localization of USRPs after pulmonary delivery in orthotopic H358-Luc tumor mouse model. (i) Fluorescence tomography imaging of mice 1, 5, or 24 hr after pulmonary administration or IV injection of USRPs (top), with bioluminescence and fluorescence imaging performed on isolated lungs showcasing colocalization of tumor cells with the USRPs at the same time points (bottom). ii) Biodistribution of USRPs in mice 24 hr after pulmonary administration or IV injection, showing enhanced accumulation in lung and tissue tumors followed by kidneys with little retention comparatively in the liver. iii) Before (top) and after (bottom) pulmonary administration of USRPs allows for detection of lung cancer tumors via magnetic resonance imaging (MRI) imaging. (c) Survival curve of H358 tumor-bearing mice without treatment (n = 6), after one irradiation (n = 11), or after USRP administration followed by one irradiation 24 hr later (n = 11), showing longer mean survival time for mice treated with USRPs and irradiation. (Reprinted with permission from Morlieras et al. (2013) and Dufort et al. (2015). Copyright 2013 American Chemical Society and Copyright 2015 John Wiley and Sons)