Phagocytosis checkpoints, especially targeting CD47, have shown encouraging
therapeutic effects. However, there are currently many shortcomings and challenges with immune checkpoint blockades (ICBs). Inspired by the phenomenon of molecular self-assembly, we modify the CD47 targeting
peptide (
4N1K) onto the self-assembled
peptide FY4, as well as the concatenation of PEG at the other terminal via the AZO group to construct
hypoxia-responsive nanoparticles (PEG-AZO-FY4-4N1K, PAP NPs), utilizing the
peptide as a part of the anti-
tumor therapy machine. After degradation, PAP NPs can self-assemble to form fibrous networks and anchor CD47 on the surface of
tumor cells, promoting their recognition and phagocytosis by macrophages and relieving immune escape. Self-assembled
peptides can interweave on the surface of
tumor cells, fully exploiting their morphological advantages to impede normal cell interaction and
metastasis. The PAP NPs work synergistically with
Doxorubicin (DOX) to further maximize the efficacy of chemoimmunotherapy. In conclusion, this strategy pioneers the progress of self-assembled
peptides in biomedicine and promises a novel breakthrough in the development of checkpoint inhibitor
therapies.