CMFn@OXA NPs achieved the tumor-targeted release of CLPoo2 and OXA in subcutaneous MC38 tumors in the following manner: upon reaching the TME by the EPR effect, CLPoo2 was liberated through cleavage of the peptide linker by matrix metalloproteinases abundant in the TME, allowing it to block PD-1/PD-L1 interactions within the tumor; OXA was released upon NP internalization, presumably through TfR1-mediated endocytosis, to elicit tumor killing. Here, TFRC is linked to neoplasm.