Since the emergence of the COVID-19 pandemic, mRNA vaccines have garnered significant attention. Delivery systems affect the effectiveness of mRNA vaccines, yet there remains a scarcity of vectors that can achieve safe and efficient delivery of mRNA. We took advantage of self-assembled glycopeptides (SAPs) to develop a vector named Man-MPm, which was coupled with mannose and manganese ions to achieve lymph node targeting and STING pathway activation. The Man-MPm-based mRNA vaccine exhibited high biosafety across various administration routes, eliciting robust antigen-specific immune responses within lymph nodes. Due to the elevated antitumor immunity, Man-MPm significantly suppressed tumor growth and extended the survival period of mice in melanoma prevention and treatment models as well as in a colon cancer model. Our findings show that Man-MPm addresses the challenges to safety and effectiveness associated with mRNA delivery by incorporating a lymph node-targeting ligand and a STING pathway agonist onto highly biocompatible SAP, and Man-MPm holds great potential for developing mRNA tumor vaccines.
