Melanin-like polydopamine nanoparticles mediating anti-inflammatory and rescuing synaptic loss for inflammatory depression therapy

Abstract

Abstract Inflammatory depression is closely related to the activation of the immune system in the peripheral and central nervous system (CNS). Due to the lack of drugs, the treatment of inflammatory depression has been an urgent problem to be solved. According to the anti-oxidative and anti-inflammatory properties, melanin-like polydopamine nanoparticles (PDA NPs), may have a good therapeutic effect on the inflammatory depression. Hence, we investigated the therapeutic effect of PDA NPs on lipopolysaccharide (LPS)-induced inflammatory depression in this study. The PDA NPs with diameter of ~250 nm were prepared by the simplest one-step synthesis method. Applying these PDA NPs to the LPS-induced inflammatory depression mice model confirmed that PDA NPs significantly reversed the depression behavior of mice. Further exploration found that, therapeutic effects of PDA NPs were attributed to their antagonism to the peripheral inflammation induced by LPS. More importantly, PDA NPs also crossed the blood-brain barrier to reach the CNS, and inhibited microglial activation via the TLR4/NF-κB signaling pathway, restoring neuronal synapse loss, which consequently attenuated depression-like behaviors induced by LPS. The PDA NPs were also confirmed to show good biocompatibility both in vivo and in vitro. Our study therefore provided the great promise of PDA NPs as a biocompatible nano-drug in rescuing inflammatory depression.