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

[BACKGROUND] Advanced gastric cancer remains a significant global health challenge, with limited therapeutic options available. In contrast, immunotherapy have emerged as promising alternatives, offering greater potency in treating advanced gastric cancer. However, the development of novel and efficient immunotherapeutic strategy is crucial to enhance the body's immune response against gastric cancer.

[METHODS] This study developed a single-injection peptide hydrogel-based nanovaccine therapy for gastric cancer treatment. The therapy utilizes a RADA peptide hydrogel, which is sensitive to metal ion concentration, to encapsulate manganese ions and HPPS nanovaccines. The HPPS nanovaccines contain antigen peptide and CpG-ODN, designed to activate both the toll-like receptor 9 (TLR9) and cGAS-STING signaling pathways in antigen-presenting cells. This design aims to facilitate a stable and sustained release of the nanovaccine, thereby enhancing the body's effective recognition and response to antigens.

[RESULTS] The efficacy of the system was confirmed using the model antigen OVA and the gastric cancer-specific antigen MG7-related peptide. The results demonstrated that the nanovaccine effectively activated the immune response, leading to enhanced recognition and response to the antigens. This activation of both TLR9 and cGAS-STING pathways in antigen-presenting cells was crucial for the observed immune response, highlighting the potential of this approach to stimulate a robust and sustained immune response against gastric cancer.

[CONCLUSIONS] This study presents a novel strategy for clinical anti-tumor vaccine administration, offering a promising approach for the prevention and treatment of gastric cancer. The single-injection peptide hydrogel-based nanovaccine system provides a convenient and effective method to enhance the body's immune response against gastric cancer. This approach could potentially be expanded to other types of cancer, providing a versatile platform for cancer immunotherapy.