On-demand phototoxicity inhibition of sensitizers and H2S-triggered in-situ activation for precise therapy of colon cancer

Conventional photo/sonosensitizers act on foci and normal tissues with limited selectivity, leading to severe skin and retina phototoxicity. Here we present a copper-hematoporphyrin monomethyl ether nanoframework (CuHF) that suppresses fluorescence on healthy tissues without generating reactive oxygen species, thus preventing phototoxicity to the skin and eyes. This nanoframework can react with endogenous hydrogen sulfide in colon cancer cells to generate CuS nanoparticles and Cu-HMME complexes in situ, enabling simultaneous photothermal and sonodynamic therapies. By leveraging strengths from coordination chemistry, material synthesis, and photochemistry, our study provides insight into the rational design of prodrug-like photosensitizers for high-precision targeted cancer therapy.