Zein nanoparticles loaded with chloroquine improve functional recovery and attenuate neuroinflammation after spinal cord injury

Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders

“…[31] A commonly used approach to stimulate M2 activation in microglia involves the use of polymeric NPs combined with natural components, such as hesperetin or zein. [255,256] Hesperetin, known for its antioxidant and anti-inflammatory properties, [257] reduces the number of reactive neutrophil and astrocyte levels, promotes Tregs production, and converts M1 microglia into M2. To TBI, a nanodrug called T-Hes, composed of 5hydroxytryptamine (5-HT), poly(lactide-glycolide) -PEG-COOH (PLGA-PEG-COOH), and loaded with hesperetin, was designed to efficiently target neutrophils.…”

“…In addition, the treatment with Zein-CQ NPs caused a decrement in the expression levels of the proinflammatory factors IL-6 and TNF-𝛼, suggesting a transition of microglia from M1 to M2 phenotype, thus promoting an antiinflammatory microenvironment. [256] We already discussed the potentiality of ferritin-based nanostructures in the context of M1 microglia polarization; HFr NPs composed of self-assembled hollow structures have also found application as microglia M2 polarization agents. These NPs can easily encapsulate drugs and target specific receptors, such as the TfR1 expressed on brain capillary endothelial cells, allowing them to cross the BBB and to deliver their cargo to the CNS.…”

“…Furthermore, in in vivo studies, T-Hes reduced the expression of pro-inflammatory cytokines like IL-1𝛽 and TNF 𝛼, while increasing anti-inflammatory cytokines. [255] Comparable results were achieved by exploiting chloroquineloaded zein NPs (Zein-CQ NPs), nanostructures composed of zein, a plant-derived protein acting as a natural polymer, and chloroquine, an antimalarial drug [256] Zein-CQ NPs have shown promising results in improving functional recovery and reducing neuroinflammation after spinal cord injury (SCI). In particular, the treatment with Zein-CQ NPs resulted into a decreased release of pro-inflammatory factors and into an increased expression of M2-related markers both in vitro and in vivo.…”

“…In addition, the treatment with Zein‐CQ NPs caused a decrement in the expression levels of the pro‐inflammatory factors IL‐6 and TNF‐α, suggesting a transition of microglia from M1 to M2 phenotype, thus promoting an anti‐inflammatory microenvironment. [ 256 ]…”