Abstract
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 (AsV), aminooxyacetic acid (AOAA), and copper ion (Cu2+) are innovatively self-assembled via coordination with high loading content and good stability. AsV in pegylated arsenic nanosheets (CAA-PEG NSs) is rapidly released and reduced to trivalent arsenic (AsIII) to exert its chemotherapy in the local tumor. Furthermore, the immunosuppressive microenvironment is thoroughly remodeled via H2S depletion of AsV to AsIII 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.