Longevity & AgingGold Nanocages Deliver Dual-Action Antidepressant Payload Deep Into the Brain
Researchers at Tongji University engineered gold nanocages (AuNCs) loaded with the VGF-derived neuropeptide TLQP21 and sealed with N-acetylcysteine (NAC) via gold-sulfur bonding, creating a nanoparticle called TNNC. In a chronic unpredictable mild stress (CUMS) mouse model of depression, TNNC reduced ROS levels in the brain, reversed depression-like behaviors, and modulated microglial activation and synaptic pruning. The NAC shell scavenges excess reactive oxygen species; its consumption under oxidative stress conditions then triggers TLQP21 release. TLQP21 acts on complement receptors C1qR and C3aR1 on microglia, suppressing downstream inflammatory signals P2Y12 and P2Y6. The study demonstrates a bioinspired, multi-target nanomedicine strategy addressing both oxidative stress and neurotrophic dysregulation in major depressive disorder.