Tailoring Polydopamine Nanoparticle Size Through Synthesis Conditions and Defining Their Antioxidant and Neuroprotective Efficacy

Introduction: Oxidative stress is a central pathological process in neurodegenerative diseases, driving the need for neuroprotective agents capable of scavenging reactive oxygen species (ROS). Polydopamine nanoparticles (PDA) hold promise due to their antioxidant properties, but their biomedical application has been limited by challenges in achieving precise size control. Methods: We established a controllable synthesis of PDA by systematically optimizing the alkaline polymerization parameters, including pH, temperature, and reaction time. We also evaluated their antioxidant and neuroprotective efficacy. Results: This approach yielded monodisperse, spherical PDA with a diameter of approximately 60 nm. The synthesized NPs exhibited potent ROS-scavenging capacity, effectively protected neuronal cells from oxidative stress, and promoted microglial polarization from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. Discussion: Our study not only systematically establishes the technical parameters for the controlled preparation of PDA but also elucidates the dual mechanisms of antioxidant activity and immunomodulation. Those results demonstrate their potential as efficient neuroprotective nanotherapeutics, while providing a solid theoretical and experimental foundation for related drug development.