Peptide hydrogel platform encapsulating manganese ions and high-density lipoprotein nanoparticle-mimicking nanovaccines for the prevention and treatment of gastric cancer

While chemotherapy and radiotherapy may alleviate symptoms and prolong survival in patients with advanced gastric cancer, their efficacy is constrained. In contrast, immunotherapies, including immune checkpoint inhibitors, T-cell transfer therapy, and therapeutic vaccines, demonstrate greater potency in treating advanced gastric cancer. This study developed a single-injection peptide hydrogel-based nanovaccine therapy for gastric cancer treatment. The therapy employs a RADA ₃₂ peptide hydrogel, sensitive to metal ion concentration, encapsulating manganese ions and HPPS nanovaccines (containing antigen peptides and CpG-ODN) to facilitate a stable, sustained release of the nanovaccine. This strategy activates both the toll-like receptor 9 and cGAS-STING signaling pathways in antigen-presenting cells, enhancing the body's effective recognition and response to antigens. The system's efficacy was confirmed using the model antigen OVA and the gastric cancer-specific antigen MG7-related peptide. This approach offers a novel strategy for clinical anti-tumor vaccine administration and may be applicable in preventing and treating gastric cancer.