Abstract
Therapeutic cancer vaccines show promise in immunotherapy but face challenges such as poor antigen delivery, insufficient immune activation, and an immunosuppressive tumor microenvironment, limiting tumor-specific cellular immunity. In this study, we present a dual-function tumor vaccine platform, MgFeZn-Layered double hydroxide (LMFZ), serving as both an antigen delivery system and immune adjuvant to enhance antitumor responses. Loaded with antigens, nanometer-sized LMFZ particles efficiently traffic to lymph nodes, promoting antigen capture by dendritic cells (DCs). LMFZ endosomal escape enables antigen cross-presentation and enhances DC maturation, boosting cytotoxic T lymphocyte proliferation and tumor infiltration. LMFZ also neutralizes tumor acidity, induces M1 polarization of macrophage, and enhances natural killer cell activity via Zn(2+) supplementation, amplifying antitumor immunity. Following two peritumoral subcutaneous injections, antigen-loaded LMFZ demonstrated significant antitumor efficacy with minimal adverse effects in a mouse model. This highlights the potential of LMFZ vaccine platform for clinical translation and offers an innovative strategy to address the limitations of current therapeutic vaccine-based immunotherapies.