Muhammad Wali, Liang Min, Wang Beiduo, Xie Jieqi, Ahmed Wajiha, Gao Changyou
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China.
Biomacromolecules. 2025 Jan 13;26(1):528-540. doi: 10.1021/acs.biomac.4c01290. Epub 2024 Dec 27.
-Acetyl cysteine (NAC) is an essential molecule that boosts acute lung injury (ALI) defense via its direct antioxidant capability. Nevertheless, the therapeutic use of NAC is limited due to its poor bioavailability and short half-life. In this study, NAC was grafted to the polyurethane consisting of poly(propylene fumarate), poly(thioketal), and 1,6-hexamethylene diisocyanate (PFTU) to reduce excessive oxidative stress and inflammatory factors in ALI. The NAC-grafted polymer nanoparticles (NPT@NPs) were prepared as a drug delivery system, which could effectively scavenge free radicals and reduce inflammation in vitro. The administration of NPT@NPs exhibited notable efficacy in ameliorating pulmonary edema, attenuating the presence of inflammatory cells, suppressing myeloperoxidase expression, diminishing the levels of pro-inflammatory cytokines, and reversing cell apoptosis in an ALI model induced by lipopolysaccharide (LPS). The NPT@NPs demonstrated significantly better efficacy compared to the free NAC in mitigating the deleterious effects of LPS on pulmonary tissue, thereby providing more effective protection against pulmonary inflammation.
N-乙酰半胱氨酸（NAC）是一种重要分子，通过其直接抗氧化能力增强对急性肺损伤（ALI）的防御。然而，由于其生物利用度低和半衰期短，NAC的治疗应用受到限制。在本研究中，将NAC接枝到由富马酸丙二醇酯、聚硫缩酮和1,6-六亚甲基二异氰酸酯（PFTU）组成的聚氨酯上，以减少ALI中过度的氧化应激和炎症因子。制备了NAC接枝聚合物纳米颗粒（NPT@NPs）作为药物递送系统，其在体外可有效清除自由基并减轻炎症。在脂多糖（LPS）诱导的ALI模型中，给予NPT@NPs在改善肺水肿、减少炎症细胞浸润、抑制髓过氧化物酶表达、降低促炎细胞因子水平以及逆转细胞凋亡方面显示出显著疗效。与游离NAC相比，NPT@NPs在减轻LPS对肺组织的有害影响方面表现出明显更好的疗效，从而为肺部炎症提供更有效的保护。
