Multifunctional Biomimetic Nanocarriers for Dual‐Targeted Immuno‐Gene Therapy Against Hepatocellular Carcinoma
Yupeng Sun, Yan Liu, Rui Li, Cuilin Zhang, Ming Wu, Xiaolong Zhang, Aixian Zheng, Naishun Liao, Youshi Zheng, Haipo Xu, Rui Zeng, Yongyi Zeng, Xiaolong Liu
Abstract
Growing 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.