Microglial‐Biomimetic Memantine‐Loaded Polydopamine Nanomedicines for Alleviating Depression

Depression is a common psychiatric disorder, and monoamine-based antidepressants as first-line therapy remain ineffective in some patients. The synergistic modulation of neuroinflammation and neuroplasticity could be a major strategy for treating depression. In this study, an inflammation-targeted microglial biomimetic system, PDA-Mem@M, is reported for treating depression. Microglial membrane-coated nanoparticles penetrate the blood-brain barrier and facilitate microglial targeting. Subsequently, owing to the excellent free radical-scavenging capacity, PDA-Mem@M attenuate the brain inflammatory microenvironment. After on-demand release from the nanoparticles, memantine increases the expression of brain-derived neurotrophic factors and reverses the loss of synaptic dendritic spines. Further, in vivo studies demonstrate that PDA-Mem@M effectively alleviate depression-like behaviors to a greater extent than memantine or polydopamine nanoparticles (PDA) monotherapy. This synergistic strategy, with satisfactory biosafety and strong anti-inflammatory and synaptic plasticity restoration effects, is conducive to advances in depression therapy.