Affiliation:
1. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou 350025 P. R. China
2. Mengchao Med‐X Center Fuzhou University Fuzhou 350116 P. R. China
3. College of Biological Science and Engineering Fuzhou University Fuzhou 350116 P. R. China
4. Liver Disease Center The First Affiliated Hospital of Fujian Medical University Fuzhou 350005 P. R. China
5. CAS Key Laboratory of Design and Assembly of Functional Nanostructures Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou 350002 P. R. China
Abstract
AbstractGrowing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA‐CaP@PD1‐NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long‐term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co‐delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.
Funder
National Natural Science Foundation of China