Manipulating the antioxidative capacity of melanin-like nanoparticles by involving condensation polymerization

Melanin is ubiquitous in nature and plays important roles in physiological activities especially in keeping the oxidative balance. Both natural and synthetic melanin were synthesized via the free radical polymerization of 5,6-dihydroxyindole (DHI) monomer, which may lead to the inherent compact π-conjugation stacking microstructures and finally results in limited antioxidative capacities. To address this issue, we have strived to involve condensation polymerization during the melanin synthetic process, aiming to disrupt the compact stacking microstructures and improve the total antioxidative performance. The resulting melaninlike nanoparticles (NPs) indeed possessed less compact stacking π-conjugation structures and decreased density, which further demonstrated enhanced antioxidative abilities compared with conventional melanin-like polymers such as poly-5,6-dihydroxyindole (Poly-DHI) and polydopamine (PDA). Their excellent free radical scavenging capability was further confirmed by the intracellular cell protection effects against reactive oxygen species (ROS) as well as in vivo therapy for acute diseases including acute kidney injury and acute liver injury. This work would promote future work toward new types of melanin-inspired nanomaterials with tunable and improved functions beyond nature.