Dopamine-modified hyaluronic acid (DA-HA) has been initially developed as an efficient coating and adhesion material for industrial uses. However, the biological activity and safety of DA-HA in the brain have not been explored yet. Here, we report a series of evidence that DA-HA exhibits similar functionality as dopamine (DA), but with much lower toxicity arising from autoxidation. DA-HA shows very little autoxidation even after 48-h incubation. This is profoundly different from DA and its derivatives including l-DOPA, which all induce severe neuronal death after pre-autoxidation, indicating that autoxidation is the cause of neuronal death. Furthermore, in vivo injection of DA-HA induces significantly lower toxicity compared to 6-OHDA, a well-known oxidized and toxic form of DA, and alleviates the apomorphine-induced rotational behavior in the 6-OHDA animal model of Parkinson's disease. Our study proposes that DA-HA with DA-like functionalities and minimal toxicity has a great potential to treat DA-related disease.

中文翻译：

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多巴胺修饰透明质酸（DA-HA）作为一种新型多巴胺模拟物，具有最小的自动氧化和细胞毒性


多巴胺修饰透明质酸（DA-HA）最初被开发为工业用途的高效涂层和粘附材料。然而，DA-HA在大脑中的生物活性和安全性尚未得到探索。在这里，我们报告了一系列证据，表明 DA-HA 表现出与多巴胺 (DA) 相似的功能，但自氧化引起的毒性要低得多。即使在 48 小时孵育后，DA-HA 也显示出很少的自氧化作用。这与DA及其衍生物包括l-DOPA有很大不同，它们都在预自氧化后诱导严重的神经元死亡，表明自氧化是神经元死亡的原因。此外，与 6-OHDA（一种众所周知的 DA 氧化和有毒形式）相比，体内注射 DA-HA 引起的毒性显着降低，并减轻了帕金森病 6-OHDA 动物模型中阿扑吗啡诱导的旋转行为。我们的研究表明，具有类似 DA 功能和最小毒性的 DA-HA 具有治疗 DA 相关疾病的巨大潜力。