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
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引用次数: 0
摘要
越来越多的证据证明,肿瘤通过免疫逃逸机制逃避免疫系统的识别和攻击,而PDL1/Pbrm1基因与免疫检查点阻断疗法(ICB)的不良反应或耐药性密切相关。本文开发了一种多功能仿生纳米载体(siRNA-CaP@PD1-NVs),它不仅能通过阻断PD1/PDL1轴增强免疫细胞的细胞毒活性,还能通过沉默Pbrm1/PDL1基因减少肿瘤免疫逃逸,从而显著改善肿瘤免疫抑制微环境。因此,纳米载体能促进 DC 细胞成熟,增强 CD8+ T 细胞的浸润和活性,形成长期免疫记忆,从而有效抑制肿瘤生长甚至消灭肿瘤,防止肿瘤复发和转移。总之,这项研究为 siRNA 药物、免疫佐剂和免疫检查点抑制剂的联合递送提供了一种强有力的策略,为提高当前免疫治疗方案的有效性和安全性带来了巨大希望。
Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma
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.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.