Li Cong, Li Jing, Bai Yujie, Zhang Kexin, Wang Zeyu, Zhang Yifan, Guan Qingyu, Wang Shiqi, Li Zehao, Li Zhihang, Chen Lijiang
School of Pharmaceutical Science, Liaoning University, Shenyang 110036, China; Liaoning Key Laboratory for New Drug Development, Shenyang 110036, China.
School of Pharmaceutical Science, Liaoning University, Shenyang 110036, China.
Int J Biol Macromol. 2025 Mar;297:139550. doi: 10.1016/j.ijbiomac.2025.139550. Epub 2025 Jan 6.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by severe inflammation and respiratory failure. Despite the use of dexamethasone (Dex) in treatment, challenges such as poor solubility and systemic side effects persist, highlighting the need for novel therapeutic approaches. This study introduces an innovative nanoparticle delivery system based on chitosan (CS) and polysialic acid (PSA), engineered via electrostatic assembly, to improve the targeted delivery of Dex to inflamed lung tissues. To enhance drug encapsulation and stability, novel taurine-Vitamin E succinate amphiphilic molecules (TVES and TGVES) were synthesized. The unique ability of PSA to specifically target Siglec-1 receptors on M1 macrophages-key contributors to ALI/ARDS-related inflammation-positions this system as a promising strategy for targeted pulmonary therapies. In vitro targeting of M1 macrophages and in vivo reduction of inflammation demonstrate the potential to transform treatment by delivering therapeutic agents precisely to the site of need. This cutting-edge nanoparticle platform not only holds promise for improving ALI/ARDS outcomes but also paves the way for the application of functional additives like taurine in advanced medical therapies.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是危及生命的病症，其特征为严重炎症和呼吸衰竭。尽管在治疗中使用了地塞米松（Dex），但诸如溶解度差和全身副作用等挑战仍然存在，这凸显了对新型治疗方法的需求。本研究引入了一种基于壳聚糖（CS）和聚唾液酸（PSA）的创新纳米颗粒递送系统，该系统通过静电组装构建，以改善地塞米松向炎症肺组织的靶向递送。为了提高药物包封率和稳定性，合成了新型牛磺酸-维生素E琥珀酸酯两亲分子（TVES和TGVES）。聚唾液酸特异性靶向M1巨噬细胞上Siglec-1受体（ALI/ARDS相关炎症的关键促成因素）的独特能力，使该系统成为靶向肺部治疗的一种有前景的策略。对M1巨噬细胞的体外靶向和体内炎症减轻表明，通过将治疗剂精确递送至需要部位来改变治疗方法具有潜力。这个前沿的纳米颗粒平台不仅有望改善ALI/ARDS的治疗结果，还为牛磺酸等功能性添加剂在先进医学治疗中的应用铺平了道路。
