Dopamine-Modified Hyaluronic Acid (DA-HA) As A Novel Dopamine-Mimetics With Minimal Autoxidation And Cytotoxicity

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-hour 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 can be an effective therapeutic substitute for L-DOPA in Parkinson’s disease.