Activatable self-assembled organic nanotheranostics: Aspartyl aminopeptidase triggered NIR fluorescence imaging-guided photothermal/photodynamic synergistic therapy

Phototherapy has developed as a powerful method for remedial modalities. The conventional photosensitizers are “always on” state and lack tumor targeting, which contributed to poor therapeutic effect and high toxicity. Therefore, we developed an aspartyl aminopeptidase (DNPEP) activated self-assembled organic nanoparticles (NRh-Asp NPs) with sensitive external irradiation-induced photothermal therapy and photodynamic therapy (PTT/PDT). NRh-Asp NPs can be activated to NRh–NH2 NPs by DNPEP, demonstrating strong near-infrared (NIR) fluorescence, and efficiently generating heat and singlet oxygen under the near-infrared laser. NRh-Asp NPs was successfully used for visualizing DNPEP in vitro and in vivo in NIR region, and demonstrated good synergistic anti-cancer efficacy of PDT and PTT. These results suggest that DNPEP-mediated NRh-Asp NPs are promising candidates for image-guided phototherapeutic of tumor. [Display omitted] •A novel self-assembled fluorescent probe (NRh-Asp NPs) was developed for detecting DNPEP activity and phototherapeutic therapy of tumor.•The NRh-Asp NPs exhibited high selectivity/sensitivity for DNPEP analysis with NIR fluorescent.•The fluorescence and phototherapeutic ability (PTT and PDT) of NRh-Asp NPs kept only the ON state in the tumor microenvironment.•The NRh-Asp NPs can effectively inhibit tumor growth by synergistic effects of PTT and PDT without causing damage to other organs.