Chronic pain has attracted wide interest because it is a major obstacle affecting the quality of life. Consequently, safe, efficient, and low‐addictive drugs are highly desirable. Nanoparticles (NPs) with robust anti‐oxidative stress and anti‐inflammatory properties possess therapeutic possibilities for inflammatory pain. Herein, a bioactive zeolitic imidazolate framework (ZIF)‐8‐capped superoxide dismutase (SOD) and Fe₃O₄ NPs (SOD&Fe₃O₄@ZIF‐8, SFZ) is developed to achieve enhanced catalytic, antioxidative activities, and inflammatory environment selectivity, ultimately improving analgesic efficacy. SFZ NPs reduce tert‐butyl hydroperoxide (t‐BOOH)‐induced reactive oxygen species (ROS) overproduction, thereby depressing the oxidative stress and inhibiting the lipopolysaccharide (LPS)‐induced inflammatory response in microglia. After intrathecal injection, SFZ NPs efficiently accumulate at the lumbar enlargement of the spinal cord and significantly relieve complete Freund's adjuvant (CFA)‐induced inflammatory pain in mice. Moreover, the detailed mechanism of inflammatory pain therapy via SFZ NPs is further studied, where SFZ NPs inhibit the activation of the mitogen‐activated protein kinase (MAPK)/p‐65 signaling pathway, leading to reductions in phosphorylated protein levels (p‐65, p‐ERK, p‐JNK, and p‐p38) and inflammatory factors (tumor necrosis factor [TNF]‐α, interleukin [IL]‐6, and IL‐1β), thereby preventing microglia and astrocyte activation for acesodyne. This study provides a new cascade nanoenzyme for antioxidant treatments and explores its potential applications as non‐opioid analgesics.

A combination of gene therapy and chemotherapy has recently received interest as a targeted therapy for glioma. A mesoporous silica nanoparticle (MSN)-based vehicle coated with IL13Rα2-targeted peptide (IP) using polyethylene glycol (PEG), MSN-PEG-IP (MPI), was constructed and confirmed as a potential glioma-targeted drug delivery system in vitro. In this work, tissue microarray (TMA) results revealed that IL13Rα2 was over-expressed in human glioma tissues and that high expression of IL13Rα2 in patients was associated with poor survival. Doxorubicin (DOX)-loaded MPI (MPI/D) crossed the blood–brain barrier, specifically targeting glioma cells and significantly enhancing the cellular uptake of DOX in glioma cells compared with MSN/DOX (M/D) and MSN-PEG/DOX (MP/D), whereas the normal brain was not affected. Magnetic Resonance Imaging (MRI) examinations showed that the tumour size of glioma-bearing rats in the MPI/D-treated group was much smaller than those in the M/D and MP/D treated groups. Immunofluorescence results demonstrated that MPI/D treatment induced more apoptosis and much less proliferation than the other two treatments. However, the therapeutic effect was weak when IL13Rα2 was knocked down. Furthermore, U87 cells treated with IL-13 and MPI together could increase both STAT6 and P63 expression, which attenuated glioma cell proliferation, invasion and migration compared with cells treated with IL-13 alone. The results of the subcutaneous tumour model also revealed that IL13Rα2 knockdown could hinder cell proliferation and induce more apoptosis. The promising results suggested that MPI can not only deliver DOX to glioma in a targeted manner but also occupy IL13Rα2, which can promote IL-13 binding to IL13Rα1 and activation of the JAK-STAT pathway to induce an anti-glioma effect.

We previously developed a biomaterial scaffold that could effectively provide seed cells to a lesion cavity resulting from traumatic brain injury. However, we subsequently found that few transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) are able to migrate from the scaffold to the lesion boundary. Stromal derived-cell factor-1α and its receptor chemokine (C-X-C motif) receptor (CXCR)4 are chemotactic factors that control cell migration and stem cell recruitment to target areas. Given the low expression level of CXCR4 on the hUC-MSC membrane, lentiviral vectors were used to generate hUC-MSCs stably expressing CXCR4 fused to green fluorescent protein (GFP) (hUC-MSCs(CXCR4/GFP)). We constructed a scaffold in which recombinant human brain-derived neurotrophic factor (BDNF) was linked to chitosan scaffolds with the crosslinking agent genipin (CGB scaffold). The scaffold containing hUC-MSCs(CXCR4/GFP) was transplanted into the lesion cavity of a rat brain, providing exogenous hUC-MSCs to both lesion boundary and cavity. These results demonstrate a novel strategy for inducing tissue regeneration after traumatic brain injury.

The R132H mutation in isocitrate dehydrogenase 1 (IDH1-R132H) is associated with better prognosis in glioma patients. Glioma stem cells (GSCs) in glioma are believed to be responsible for glioma growth and maintenance. However, the relation between the R132H mutation and GSCs is not fully understood. In the present study, GSC markers were detected in patients with IDH1-R132H or wild-type IDH1 (IDH1-wt) by tissue microarray immunohistochemistry (TMA-IHC). The relationship between the expression patterns of GSC markers and the clinicopathological characteristics in glioma were analyzed. To confirm this mutation's role in GSCs, the IDH1-R132H in GSCs isolated from glioblastoma patients with IDH1 mutations was overexpressed by using lentiviral constructs in vitro, and then the proliferation, differentiation, apoptosis, migration and invasion of the transfected GSCs were explored. At the molecular level, we detected Wnt/β-catenin signaling expression to verify its role in regulating the cellular properties of GSCs. The results showed that the positive rate of GSCs in patients with IDH1-R132H was significantly less than that in patients with IDH1-wt. The positive rate of GSCs was correlated with IDH1 mutation, TNM stage and poor overall survive. After transfection in vitro, IDH1-R132H overexpression led to reduced GSCs proliferation, migration and invasion, inducing apoptosis and improving GSC differentiation, accompanied by a significant reduction in activity of β-catenin. Several mediators, effectors and targets of the Wnt/β-catenin signaling were downregulated. The data demonstrate that IDH1 mutation reduces the malignant progression of glioma by causing a less aggressive phenotype of GSCs which are involved in the Wnt/β‑catenin signaling.