# N‑Acetylcysteine-Capped TLQP21-Containing Au Nanocages Alleviate Depression in Mice

## TL;DR

A new nanoparticle treatment using N-acetylcysteine and TLQP21 reduces depression-like behaviors and brain inflammation in mice.

## Contribution

A novel antioxidant Au nanocage delivers TLQP21 to target oxidative stress and microglial inflammation in depression.

## Key findings

- TNNC administration reduced MDD-like behaviors in CUMS-exposed mice.
- TLQP21 inhibited microglial activation and synaptic pruning via C1qR and C3aR1.
- TNNC effectively relieved oxidative stress in the brain.

## Abstract

Major depressive disorder (MDD) is the most prevalent
neuropsychiatric
disorder globally. Promising therapies for MDD are urgently needed
due to the limited effectiveness, delayed efficacy, and non-negligible
side effects of current treatments. Oxidative stress and neuroinflammation
have been recognized as key contributors to MDD. Here, we developed
an antioxidant N-acetylcysteine (NAC)-capped Au nanocage
(TNNC) that entrapped VGF-derived peptide TLQP21 with neuro-immunomodulatory
effects. Once internalized by cells suffering from oxidative stress,
NAC was consumed, and TLQP21 was released from TNNC. TNNC administration
alleviated MDD-like behaviors of the chronic unpredictable mild stress
(CUMS)-exposed mice and effectively relieved oxidative stress in the
brains. Moreover, TLQP21 in TNNC inhibits the activation, excessive
synaptic pruning, and inflammatory responses of microglia through
targeting the complement C1q receptor (C1qR) and complement C3a receptor
1 (C3aR1). This work provides a bioinspired strategy to target multiple
pathogenic factors in one nanoparticle for the intervention of MDD
and other diseases.