Programmable phthalocyanine-iron-based nanoreactor for fluorescence/magnetic resonance dual-modality imaging-guided sono/chemodynamic therapies

Although specific responsive theranostics biomaterials were essencial for precision medicine, the univariate responsive strategy was restricted by high false-positive rates. Herein, we designed a novel phthalocyanine-iron-based complex FeS2@PcD, as a theranostics nanoreactor, which was program-regulated by bivariate factors of H+ and H2O2 in tumor microenvironment (TME). We found that FeS2@PcD had the excellent capability of tumor fluorescence imaging (FLI), with a 52.21-fold increase in fluorescence signal by the programmable response, while the signal of the univariate factor was almost unchanged. We also revealed that FeS2@PcD reacted with H+ to release PcD and produced Fe2+, then Fe2+ was further oxidized by H2O2 to produce Fe3+, finally recovering the fluorescence of PcD whose fluorescence activity was significantly suppressed due to the photoinduced electron transfer (PET) effect. Notably, except for fluorescence signal, magnetic resonance (MR) signal and sonosensitive activity of FeS2@PcD also changed from “OFF” state to “ON” state under the programmable regulation of H+ and H2O2. The program-regulated strategy based on FeS2@PcD realized specific fluorescence and MR dual-modality imaging-guided sono/chemodynamic therapies, representing a promising precision medicine approach.