Zinc‐Organometallic Framework Vaccine Controlled‐Release Zn2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy

• DOI: 10.1002/advs.202302967
• Publication Date: 2023-07-13T11:36:17Z
• Authors: Lin Ding; Minli Liang; Yuanyuan Li; Mei Zeng; Meiting Liu; Wei Ma; Fuming Chen; Chenchen Li; Rui L. Reis; Fu‐Rong Li; Yanli Wang
• Keywords: Cancer Immunotherapy

Abstract Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason immunotherapy failure. The cyclic guanosine monophosphate‐adenosine monophosphate synthase‐stimulator of interferon genes (cGAS‐STING) pathway plays key role in activating CD8 + cells, maintaining stemness and enhancing the antitumor effect. Herein, zinc‐organometallic framework vaccine (ZPM@OVA‐CpG) prepared by self‐assembly, achieves site‐directed release Zn 2+ dendritic cell (DC) lysosomes tumor microenvironment under acidic conditions, reported. actively targets DC, significantly enhances cGAS‐STING signal, promotes DC maturation antigen cross‐presentation, induces strong activation cells. Meanwhile, reaches site, releasing , up‐regulates activity metalloproteinase‐2, degrades various collagen components ECM, effectively alleviates immune suppression, infiltration killing ZPM@OVA‐CpG solves problem low delivery efficiency weak ability, degradation ECM via first time, providing promising therapeutic platform development efficient novel vaccines.