“…Currently, imaging-guided theranostic nanosystems have garnered tremendous interest for simultaneously monitoring drug distribution and treatment processes in tumors. − Inorganic nanoparticles with superior optical characteristics, such as Au, quantum dots, CuS, upconversion nanoparticles, etc., have been extensively applied for imaging-guided therapy. − However, intricate and complex procedures were demanded to incorporate therapeutics into these nanoparticles for the lack of active binding sites. , Moreover, a majority of imaging-guided therapeutic nanoplatforms consists of “always-on” probes, which track the biodistribution of nanomaterials independent of the tumor-related factors, resulting in the nontumor-specific imaging . In contrast, the readout signal of the tumor-responsive probes can be specifically activated by the tumor-related targets (such as TME) to accurately monitor the dynamic variations in tumors for the guidance of the treatment process and the evaluation of the therapeutic efficacy. , Nevertheless, the tumor-responsive probes are incapable of tracking the real-time distribution of the material in the systemic normal tissue for the biosafety assessment on account of the inactive off-state. Therefore, the combination of tumor-activated and always-on fluorescence imaging plays an important role in monitoring the dynamic distribution of nanoplatforms in tumor and physiological systems.…”