Recently, Associate Professor Liu Qi from School of Pharmacy at our university, in collaboration with Professor Liu Yang from School of Chemistry at Nankai University, have had their academic article entitled “Precisely Activating cGAS-STING Pathway with a Novel Peptide-Based Nanoagonist to Potentiate Immune Checkpoint Blockade Cancer Immunotherapy” published in the prestigiously high-impact journal Advanced Science (IF: 15.1). The corresponding authors for this publication are Liu Qi and Liu Yang, with School of Pharmacy of our university designated as the first completion institution.
To precisely activate the cGAS-STING pathway and synergistically block programmed cell death-ligand 1 (PD-L1) for safe and efficient cancer immunotherapy, the study, for the first time, demonstrated the activation of the cGAS-STING pathway based on antimicrobial peptides, and developed a multi-stimuli-responsive multi-peptide nanomedicine (MAPN) for in vivo delivery of the antimicrobial peptide (KLA) and the PD-L1 antagonist peptide (CVR). To construct MAPN, in this study, KLA and CVR were first conjugated to polyacrylic acid diisopropylamine (PDPA) via disulfide or thioether bonds, and then self-assembled with a responsive cleavable polyethylene glycolized polymer to prevent immune clearance during blood circulation and achieve efficient tumor tissue enrichment. Subsequently, MAPN further responded to hydrogen peroxide (H2O2) in the tumor microenvironment and glutathione (GSH) in tumor cells to achieve site-specific release of KLA and CVR.