Injectable Supramolecular Hydrogel for Locoregional Immune Checkpoint Blockade and Enhanced Cancer Chemo-Immunotherapy

Abstract

Immunotherapy has revolutionized the therapeutic modalities of cancer treatment but is severely limited by a low objective response rate and the risk of immune-related side effects. Herein, an injectable supramolecular hydrogel is developed for local delivery of the ^DPPA-1 peptide (a d-peptide antagonist with a high binding affinity to programmed cell death-ligand 1 (PD-L1)) and doxorubicin (DOX). On the one hand, DOX could kill tumor cells directly and also induce immunogenic cell death to provoke the antitumor immune response. On the other hand, the ^DPPA-1 peptide could locoregionally block the PD-1/PD-L1 pathway to potentiate T-cell-mediated immune responses and minimize side effects. Eventually, by local injection of this supramolecular hydrogel, the synergistic cancer therapeutic effect was evaluated, showing promise in improving the objective response rate of immunotherapy and minimizing its systemic side effects.