摘要
树突状细胞(dendritic cells,DCs)在连接先天免疫与适应性免疫中起着关键作用,尤其在T细胞的活化和肿瘤免疫应答的调控中具有重要功能。然而,肿瘤微环境中的免疫抑制性细胞因子以及DCs内的脂质过氧化失衡,极大限制了其有效激活肿瘤特异性T细胞能力。为此,作者基于人工智能设计了一种纳米仿生药物递送平台,该平台通过将姜黄素纳米粒装载于细菌外膜囊泡(outer membrane vesicles,OMVs)中,旨在通过药物递送与免疫激活双重策略增强DCs功能。体外实验结果表明,姜黄素通过调控IRE1α-XBP1信号通路显著缓解了DCs的脂质过氧化应激,从而恢复其抗原呈递功能。此外,OMVs不仅作为高效药物载体,还作为强大的免疫激活剂,促进了DCs的成熟并增强了其肿瘤特异性免疫应答能力。本研究提出了一种提升抗肿瘤免疫治疗的新策略,并为人工智能在药物递送系统中的应用提供了新的研究视角。
Dendritic cells(DCs)play a critical role in both innate and adaptive immunity,particularly in regulating antitumor immune responses.However,immunosuppressive cytokines in the tumor microenvironment and lipid peroxidation imbalance within DCs limit their ability to activate tumor-specific T cells effectively.To address this,we developed a novel biomimetic nanodrug delivery platform using artificial intelligence(AI).This platform encapsulates curcumin nanoparticles in bacterial outer membrane vesicles(OMVs)to enhance DCs function through a dual approach:targeted drug delivery and immune activation.In vitro experiments demonstrated that curcumin reduced lipid peroxidation stress in DCs by modulating the IRE1α-XBP1 signaling pathway,thereby restoring their antigen-presenting function.Additionally,OMVs not only acted as efficient drug carriers but also as immune activators,promoting DCs maturation and enhancing tumor-specific immune responses.This study presents a promising strategy for improving antitumor immunotherapy and offers new insights into the application of AI in drug delivery systems.
作者
谢东轩
东玉灏
何仲贵
孙进
孙孟驰
XIE Dong-xuan;DONG Yu-hao;HE Zhong-gui;SUN Jin;SUN Meng-chi(Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China;School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Joint International Research Laboratory of Intelligent Drug Delivery Systems,Ministry of Education,Shenyang 110016,China)
出处
《药学学报》
北大核心
2025年第5期1525-1533,共9页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(82372111)。
关键词
人工智能
姜黄素
免疫抑制
树突状细胞
细菌外膜囊泡
artificial intelligence
curcumin
immunosuppression
dendritic cell
outer membrane vesicle
