Dopamine-modified hyaluronic acid (DA-HA) as a novel dopamine-mimetics with minimal autoxidation and cytotoxicity
Sunpil Kim,
Ye-Ji Kim,
Kyoung Hwan Park,
Kang Moo Huh,
Sun-Woong Kang,
C. Justin Lee,
Dong Ho Woo
Affiliations
Sunpil Kim
Center for Cognition and Sociality, Life Science Cluster, Institute for Basic Science (IBS), Daejeon, 34126, South Korea
Ye-Ji Kim
Human and Environmental Toxicology, University of Science and Technology (UST), Daejeon, 34114, South Korea; Department of Advanced Toxicology Research, Korea Institute of Toxicology (KIT), KRICT, Daejeon, 34114, South Korea
Kyoung Hwan Park
Department of Polymer Science and Engineering, Chungnam National University (CNU), Daejeon, 34134, South Korea; Research Group for Biomimetic Advanced Technology, Korea Institute of Toxicology (KIT), KRICT, Daejeon, 34114, South Korea
Kang Moo Huh
Department of Polymer Science and Engineering, Chungnam National University (CNU), Daejeon, 34134, South Korea
Sun-Woong Kang
Human and Environmental Toxicology, University of Science and Technology (UST), Daejeon, 34114, South Korea; Research Group for Biomimetic Advanced Technology, Korea Institute of Toxicology (KIT), KRICT, Daejeon, 34114, South Korea
C. Justin Lee
Center for Cognition and Sociality, Life Science Cluster, Institute for Basic Science (IBS), Daejeon, 34126, South Korea; Corresponding author. Center for Cognition and Sociality, Life Science Cluster, Institute for Basic Science, Daejeon, 34126, South Korea.
Dong Ho Woo
Human and Environmental Toxicology, University of Science and Technology (UST), Daejeon, 34114, South Korea; Department of Advanced Toxicology Research, Korea Institute of Toxicology (KIT), KRICT, Daejeon, 34114, South Korea; Corresponding author. Department of Advanced Toxicology Research, Korea Institute of Toxicology, KRICT, Daejeon, 34114, South Korea.
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.
