Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, 96 Jinzhai Road, Hefei 230026, China.
ACS Nano. 2024 Mar 12;18(10):7346-7362. doi: 10.1021/acsnano.3c08662. Epub 2024 Feb 28.
The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.
创伤性脊髓损伤（SCI）后的微环境涉及复杂的病理过程，包括氧化应激升高、脂质过氧化产生的蓄积反应性醛、过度的免疫细胞浸润等。不幸的是，大多数现有的神经保护疗法都无法应对 SCI 复杂的病理生理学，导致治疗效果不佳。在这里，我们开发了一种简便的反应诱导自组装方法来制备醛清除肽（PAH）-姜黄素缀合物纳米组装体（命名为 PFCN），用于 SCI 的联合神经保护。制备的 PFCN 可以响应氧化和酸性 SCI 微环境释放 PAH 和姜黄素。随后，PFCN 通过清除神经元中的有毒醛以及活性氮和氧物种、调节小胶质细胞 M1/M2 极化和下调炎症相关细胞因子的表达来抑制神经炎症，表现出有效的神经保护作用。PFCN 的静脉给药可显著改善损伤脊髓的恶性微环境，保护神经元，并促进挫伤性 SCI 大鼠模型的运动功能恢复。
