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Background  Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H 2 S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H 2 S and the regulation of the enzymes on the H 2 S pathways are of great significance for colorectal cancer therapy.    Methods  Here, we investigated the H 2 S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H 2 S in colorectal cancer. Accordingly, we developed an H 2 S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer.    Results  Owing to its excellent H 2 S scavenging ability, VZnO could effectively reduce H 2 S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H 2 S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H 2 S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H 2 S rich cancers, such as the 4T1 breast cancer model.    Conclusions  We anticipate that the H 2 S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.    Graphic abstractSupplementary Information  The online version contains supplementary material available at 10.1186/s12951-021-01069-y.

Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer