In situ valence-transited arsenic nanosheets for multi-modal therapy of colorectal cancer

Late-stage and advanced colorectal cancer (CRC) often prove to be resistant to current treatment regimens, due to the evolving tumor microenvironment. Chemotherapy-dominated multi-modal therapeutic strategies based on the specific CRC microenvironment open a new horizon for eradicating colorectal tumors. Here, in situ valence-transited arsenic nanosheets are developed as a multi-modal therapeutic platform by responding to the H₂S-enriched CRC microenvironment. Carrier-free pegylated nanosheets of pentavalent arsenic (As^V), aminooxyacetic acid (AOAA), and copper ion (Cu²⁺) are innovatively self-assembled via coordination with high loading content and good stability. As^V in pegylated arsenic nanosheets (CAA-PEG NSs) is rapidly released and reduced to trivalent arsenic (As^III) to exert its chemotherapy in the local tumor. Furthermore, the immunosuppressive microenvironment is thoroughly remodeled via H₂S depletion of As^V to As^III conversion and impairment of H₂S production by AOAA. Additionally, the in situ produced ultrasmall CuS nanoparticles exhibit photothermal activity against CRC under the guidance of photoacoustic imaging. This multi-modal therapeutic strategy, dominated by chemotherapy, completely inhibits CRC progression and prevents its relapse.