Cross-linked catechol-bearing poly(γ-glutamic acid) self-aggregates with antioxidant activity

Reactive oxygen species (ROS) are mainly formed by metabolism of oxygen in the human body and play essential roles in cell signaling, pathogen defense, and homeostasis. However, elevated levels of these species have been linked to inflammatory diseases such as arthritis as well as tumor growth. For this reason, the therapeutic use of antioxidants, compounds capable of inactivating these ROS species, has attracted growing attention. In spite of the ROS-scavenging activity, their low stability as well as poorly controlled pharmacokinetics is a major limitation in antioxidant therapy. To overcome this limitation, we recently reported that polymeric micelles having ROS-scavenging catechol moieties showed increased oxidation stability as compared to the small catechol compound dopamine. This micelles efficiently inhibited angiogenesis by scavenging endogenous ROS. Here, we present the preparation of antioxidant nanoparticles formed by self-assembly of amphiphilic dopamine-grafted poly(γ-glutamic acid). The nanoparticles formed by interaction of the catechol groups via physical interaction and the size of the nanoparticles could be controlled in the range of 25–130 nm by changing the catechol/carboxylate molar ratio as shown by dynamic light scattering. To improve colloidal stability, the formed nanoparticles were chemically cross-linked by the oxidative coupling of the catechol groups at high pH as shown by atomic force microscopy. The prepared antioxidant nanoparticles were capable of scavenging ROS like H₂O₂ and may find application in antioxidant therapy.