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.