1 research outputs found
Redox Potential-Sensitive <i>N</i>‑Acetyl Cysteine-Prodrug Nanoparticles Inhibit the Activation of Microglia and Improve Neuronal Survival
One hallmark of neuroinflammation
is the activation of microglia,
which triggers the production and release of reactive oxygen species
(ROS), nitrate, nitrite, and cytokines. <i>N</i>-Acetyl
cysteine (NAC) is a free radical scavenger that is involved in the
intracellular and extracellular detoxification of reactive oxygen
species in the brain. However, the clinical application of NAC is
limited by its low bioavailability and short half-life. Herein, NAC
was conjugated to a polymer through a disulfide bond to form a NAC-prodrug
nanoparticle (NAC-NP). Dynamic light scattering found that the NAC-NP
has a size of around 50 nm. In vitro studies revealed that the release
of NAC from NAC-NP is responsive to its environmental redox potential.
For mimicking neuroinflammation in vitro, microglial cells were stimulated
by a lipopolysaccharide (LPS), and the effect of NAC-NP on activated
microglia was investigated. The study found that the morphology as
well as the expression of microgliosis marker Iba-1 of the cells treated
with NAC-NPs and LPS were close to those of control cells, indicating
that NAC-NPs can inhibit the activation of microglia stimulated by
LPS. Compared with free NAC, the production of ROS, NO<sub>3</sub>-, NO<sub>2</sub>-, tumor necrosis factor-α (TNF-α),
and interleukin (IL)-1β from the LPS-stimulated microglia was
considerably decreased when the cells were pretreated with NAC-NPs.
Furthermore, LPS-induced microglial phagocytocis of neurons was inhibited
in the presence of NAC-NPs. These results indicated that NAC-NPs are
more effective than free NAC for reversing the effect of LPS on microglia
and subsequently protecting neurons