The effectiveness of
cancer immunotherapy is impaired by the dysfunctional vasculature of
tumors. Created
hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in
tumor tissue. Structural and functional normalization of abnormal
tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the
hypoxia in the
tumor site and increasing infiltration of antitumor T cells. Taking advantage of
peptide amphiphiles, herein, a novel
peptide amphiphile nanoparticle composed of an antiangiogenic
peptide (FSEC) and an immune checkpoint blocking
peptide (D PPA) is designed and characterized. FSEC
peptide is known to be involved in vessel normalization of
tumors in vivo. D PPA is an inhibitory
peptide of the PD-1/PD-L1 immune checkpoint pathway. The
peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of
tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on
tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD-L1 reactivates effective immune responses to the
tumors. In summary, the current study provides a new perspective on the regulation of
tumor vessel normalization and
immunotherapy based on functional
peptide nanoparticles as nanomedicine for improved therapeutic purposes.