一种逻辑门控纳米平台时空协调免疫代谢重编程与成骨用于糖尿病牙周再生
A logic-gated nanoplatform spatiotemporally orchestrates immunometabolic reprogramming and osteogenesis for diabetic periodontal regeneration.
摘要(中文译文)
在糖尿病牙周炎（DPD）中实现牙周再生受到过度氧化应激与适应性免疫功能障碍之间自我延续的恶性循环的阻碍。本研究利用临床样本、多组学分析和DPD大鼠模型，发现了氧化应激与CD4 T细胞失调之间的关联。该过程以活性氧（ROS）蓄积和Th17/Treg失衡为特征，可能促进牙槽骨的进行性丧失。为调控这一病理过程，我们构建了一种逻辑门控水凝胶-纳米颗粒杂合系统，用于活性维生素D（AVD）的层级递送。该平台具有动态硼酸酯交联网络，可作为ROS响应开关。在暴露于氧化微环境时，基质发生程序性降解以清除ROS，触发抗体功能化纳米颗粒的快速释放。这些纳米颗粒选择性靶向CD4 T细胞并将AVD递送至细胞内，在其中调节线粒体稳态和代谢信号通路，从而恢复T细胞免疫稳态。在此免疫重置之后，系统转入第二阶段，由多孔铜基金属有机框架持续释放AVD和成骨性Cu，以支持长期骨重塑。通过整合氧化还原响应性驱动、靶向免疫代谢调控和持续骨免疫调节，该层级系统为糖尿病牙周炎的牙周再生提供了一种有前景的治疗策略。
Abstract
Achieving periodontal regeneration in diabetic periodontitis (DPD) is hindered by a self-perpetuating vicious cycle of excessive oxidative stress and adaptive immune dysfunction. Here, using clinical samples, multi-omics profiling, and DPD rat model, we identified an association between oxidative stress and CD4 T cell dysregulation. This process was characterized by reactive oxygen species (ROS) accumulation and Th17/Treg imbalance, which may contribute to progressive alveolar bone loss. To modulate this pathological process, we engineered a logic-gated hydrogel-nanoparticle hybrid system for hierarchical delivery of active vitamin D (AVD). This platform features a dynamic boronic ester crosslinked network that functions as a ROS-responsive switch. Upon exposure to the oxidative microenvironment, the matrix undergoes programmed degradation to scavenge ROS, triggering the rapid release of antibody-functionalized nanoparticles. These nanoparticles selectively target CD4 T cells and deliver AVD intracellularly, where it modulates mitochondrial homeostasis and metabolic signaling pathways, thereby restoring T-cell immune homeostasis. Following this immune reset, the system transitions into a second phase where porous copper-based metal-organic frameworks provide sustained release of AVD and osteogenic Cu to support long-term bone remodeling. By integrating redox-responsive actuation, targeted immunometabolic regulation, and sustained osteoimmunomodulation, this hierarchical system provides a promising therapeutic strategy for periodontal regeneration in diabetic periodontitis.
如何引用
AMA
Yujun Jiang, Shuyun Liu, Xiaolin Li, Lu Han, Hongrui Liu, Minqi Li. A logic-gated nanoplatform spatiotemporally orchestrates immunometabolic reprogramming and osteogenesis for diabetic periodontal regeneration.. Bioactive materials. 2027; doi:10.1016/j.bioactmat.2026.08.051.
APA
Yujun Jiang, Shuyun Liu, Xiaolin Li, Lu Han, Hongrui Liu, Minqi Li (2027). A logic-gated nanoplatform spatiotemporally orchestrates immunometabolic reprogramming and osteogenesis for diabetic periodontal regeneration.. Bioactive materials. https://doi.org/10.1016/j.bioactmat.2026.08.051
GB/T 7714
Yujun Jiang, Shuyun Liu, Xiaolin Li, Lu Han, Hongrui Liu, Minqi Li. A logic-gated nanoplatform spatiotemporally orchestrates immunometabolic reprogramming and osteogenesis for diabetic periodontal regeneration.[J]. Bioactive materials, 2027 doi:10.1016/j.bioactmat.2026.08.051.
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