基于人工智能设计的载药细菌外膜囊泡用于体外激活树突状细胞的研究
Artificial intelligence-designing drug-loaded bacterial outer membrane vesicles for in vitro activation of dendritic cells
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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。Abstract: 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.
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