{"title":"Polyphenol-Based Self-Assembled Nanomedicine for a Three-Pronged Approach to Reversing Tumor Immunosuppression.","authors":"Zimu Li, Zirui Chen, Kexin Shi, Ping Huang, Wenfeng Zeng, Qili Huang, Jingwen Peng, Li Yang, Hongzhong Chen, Yanli Zhao, Xiaowei Zeng","doi":"10.1002/adhm.202402127","DOIUrl":null,"url":null,"abstract":"<p><p>The challenges of multi-pathway immune resistance and systemic toxicity caused by the direct injection of immune checkpoint inhibitors are critical factors that compromise the effectiveness of clinical immune checkpoint blockade therapy. In this context, natural polyphenols have been employed as the primary component to construct a targeted and acid-responsive PD-L1 antibody (αPD-L1) delivery nanoplatform. This platform incorporates garcinol, an inhibitor of the Nuclear Factor Kappa-B (NF-κB) signaling pathway, to regulate pro-tumor immune escape cytokines and regulatory T cells. Additionally, the nanoplatform has been verified to induce immunogenic cell death (ICD), which promotes the maturation of dendritic cells and enhances the activity of cytotoxic T lymphocytes. In vivo and in vitro experimental results demonstrated that the nanoplatform can boost the immune response through a PD-L1 and NF-κB blocking/ICD inducing three-pronged strategy, thereby effectively combating tumor growth and metastasis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":null,"pages":null},"PeriodicalIF":10.0000,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Healthcare Materials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1002/adhm.202402127","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
The challenges of multi-pathway immune resistance and systemic toxicity caused by the direct injection of immune checkpoint inhibitors are critical factors that compromise the effectiveness of clinical immune checkpoint blockade therapy. In this context, natural polyphenols have been employed as the primary component to construct a targeted and acid-responsive PD-L1 antibody (αPD-L1) delivery nanoplatform. This platform incorporates garcinol, an inhibitor of the Nuclear Factor Kappa-B (NF-κB) signaling pathway, to regulate pro-tumor immune escape cytokines and regulatory T cells. Additionally, the nanoplatform has been verified to induce immunogenic cell death (ICD), which promotes the maturation of dendritic cells and enhances the activity of cytotoxic T lymphocytes. In vivo and in vitro experimental results demonstrated that the nanoplatform can boost the immune response through a PD-L1 and NF-κB blocking/ICD inducing three-pronged strategy, thereby effectively combating tumor growth and metastasis.
直接注射免疫检查点抑制剂所引起的多途径免疫耐受和全身毒性是影响临床免疫检查点阻断疗法有效性的关键因素。在这种情况下,人们采用天然多酚作为主要成分,构建了一种具有靶向性和酸响应性的 PD-L1 抗体(αPD-L1)递送纳米平台。该平台结合了核因子卡巴-B(NF-κB)信号通路抑制剂加西诺酯,以调节促肿瘤免疫逃逸细胞因子和调节性 T 细胞。此外,纳米平台还能诱导免疫原性细胞死亡(ICD),从而促进树突状细胞的成熟并增强细胞毒性 T 淋巴细胞的活性。体内和体外实验结果表明,该纳米平台可通过PD-L1和NF-κB阻断/诱导ICD三管齐下的策略提高免疫反应,从而有效对抗肿瘤的生长和转移。
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.