Wang Lei, Li Zhong-Yao, Zhong Chong-Lei, Teng Zi-Yang, Wang Bin, Rehman Asma, Han Li-Wen, Zeng Ke-Wu, Zhang Ji-Guo, Lu Zhi-Yuan
School of Pharmaceutical Sciences & Institute of Materia Medica, State Key Laboratory of Advanced Drug Delivery and Release Systems, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, China.
Department of Andrology, Guang'Anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100053, China.
Chin Med. 2025 Apr 11;20(1):49. doi: 10.1186/s13020-025-01103-3.
Sepsis is a life-threatening infectious disease characterized by an uncontrolled inflammatory response and consequent multi-organ dysfunction. The kidneys, as primary excretory organs with high blood flow, are particularly susceptible to damage during sepsis. Nonetheless, the existing treatment options for sepsis-associated acute kidney injury (SA-AKI) are still restricted. Nanomedicine, especially carbon dots (CDs), has attracted considerable interest lately for outstanding biomedical characteristics.
To avoid the generation of toxic effects, the natural CDs derived from Ziziphi Spinosae Semen (Z-CDs) were synthesized employing a hydrothermal method. The free radical scavenging capabilities of Z-CDs were evaluated by utilizing ABTS assay, NBT method, and Fenton reaction. A lipopolysaccharide (LPS)-stimulated RAW 264.7 cell model was used to explore the therapeutic potential of Z-CDs on cellular oxidative stress and inflammation. The CuSO-induced zebrafish inflammation model and LPS-exposed SA-AKI mouse model were employed to assess the therapeutic efficacy of Z-CDs in vivo.
The synthesized Z-CDs exhibited distinctive unsaturated surface functional groups, which confer exceptional biocompatibility and the ability to scavenge free radicals. Moreover, Z-CDs were particularly effective in eliminating excess reactive oxygen species (ROS) in cells, thus protecting mitochondrial function from oxidative damage. Notably, Z-CDs have demonstrated significant therapeutic benefits in protecting kidney tissue in SA-AKI mouse model with minimizing side effects. In mechanism, Z-CDs effectively reduced ROS production, thereby alleviating inflammatory responses in macrophages through the suppression of the NF-κB pathway.
This study developed a multifunctional nanomedicine derived from traditional medicinal herb, providing a promising pathway for the advancement of innovative drug therapies to treat SA-AKI.
脓毒症是一种危及生命的传染病，其特征为不受控制的炎症反应及随之而来的多器官功能障碍。肾脏作为具有高血流量的主要排泄器官，在脓毒症期间特别容易受到损伤。尽管如此，脓毒症相关急性肾损伤（SA-AKI）的现有治疗选择仍然有限。纳米医学，尤其是碳点（CDs），因其出色的生物医学特性最近引起了相当大的关注。
为避免产生毒性作用，采用水热法合成了源自酸枣仁的天然碳点（Z-CDs）。利用ABTS法、NBT法和芬顿反应评估Z-CDs的自由基清除能力。使用脂多糖（LPS）刺激的RAW 264.7细胞模型来探索Z-CDs对细胞氧化应激和炎症的治疗潜力。采用硫酸铜诱导的斑马鱼炎症模型和LPS暴露的SA-AKI小鼠模型来评估Z-CDs在体内的治疗效果。
合成的Z-CDs表现出独特的不饱和表面官能团，赋予其卓越的生物相容性和自由基清除能力。此外，Z-CDs在消除细胞内过量的活性氧（ROS）方面特别有效，从而保护线粒体功能免受氧化损伤。值得注意的是，Z-CDs在SA-AKI小鼠模型中保护肾脏组织方面显示出显著的治疗益处，且副作用最小。在机制上，Z-CDs有效减少ROS产生，从而通过抑制NF-κB途径减轻巨噬细胞中的炎症反应。
本研究开发了一种源自传统草药的多功能纳米药物，为推进治疗SA-AKI的创新药物疗法提供了一条有前景的途径。
