To summarize, we have designed and synthesized a novel strategy of coupling PD-L1 polypeptide with cytotoxic agent for tumor-targeted therapy in colon cancer, in which a proteolysis resistant PD-L1 targeting peptide PPA1 is conjugated with DOX by a pH sensitive linker, which could trigger the release of drugs near tumor tissues. Here, CD274 is linked to colonic neoplasm.