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International Journal of Nanomedicine · 2025 · IF 6.5

Regulation of Neuroimmune Microenvironment by PLA/GO/Anti-TNF-α Composite to Enhance Neurological Repair After Spinal Cord Injury

Yishu Liu,Jingsong Liu,Yangyang Wang,Yubo Zhang,Zhibin Peng,Pengfei Li,Mi Li,Bing Xue,Yansong Wang

Introduction: Spinal cord injury (SCI) is a severe neurological condition with limited treatment options. Polylactic acid (PLA)+graphene oxide (GO)+anti-TNF-α (Ab) composites have shown potential in regulating immune responses and promoting neural repair.Methods: Electrospinning PLA+GO+Ab materials were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and X-ray diffraction (XRD). Their effects on neural stem cells (NSCs) and macrophage polarization were evaluated through in vitro assays, including proliferation, migration, differentiation, and flow cytometry. A rat SCI model was used to assess motor function recovery and histological changes.Results: PLA+GO+Ab promoted NSC proliferation, migration, and differentiation while inducing macrophage polarization toward the M2 phenotype, reducing inflammation. In the SCI model, PLA+GO+Ab treatment enhanced motor function recovery, reduced spinal cord damage, and promoted axonal regeneration and oligodendrocyte maturation. RNA sequencing identified activation of the Rap1 signaling pathway, contributing to these effects.Discussion: PLA+GO+Ab composites effectively modulate the neuroimmune microenvironment, supporting SCI recovery by promoting neural repair and immune regulation. These findings suggest its potential as a therapeutic biomaterial for SCI treatment.

CAS / MDL: 920-66-1
研究领域: 生物医学工程 · 神经科学 · 免疫学
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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Oral delivery of infliximab using nano-in-microparticles for the treatment of inflammatory bowel disease

Xin Li,Mengli Yu,Zhuo Zhu,Chao Lu,Meng Jin,Yuefeng Rao,Qingwei Zhao,Xiaoyang Lu,Chaohui Yu

The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine . In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.

CAS / MDL: 9005-38-3
研究领域: 药学 · 胃肠病学 · 纳米技术 · 药物递送系统
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Surface Coating of Pulmonary siRNA Delivery Vectors Enabling Mucus Penetration, Cell Targeting, and Intracellular Radical Scavenging for Enhanced Acute Lung Injury Therapy

Jiaojiao Zhu,Man Guo,Yanhui Cui,Yingcai Meng,Jinsong Ding,Wenbin Zeng,Wenhu Zhou

Pulmonary delivery of anti-inflammatory siRNA presents a promising approach for localized therapy of acute lung injury (ALI), while polycationic vectors can be easily trapped by the negatively charged airway mucin glycoproteins and arbitrarily internalized by epithelial cells with nontargetability for immunological clearance. Herein, we report a material, the dopamine (DA)-grafted hyaluronic acid (HA–DA), coating on an anti-TNF-α vector to address these limitations. HA–DA was simply synthesized and facilely coated on poly(β-amino ester) (BP)-based siRNA vectors via electrostatic attraction. The resulting HA–DA/BP/siRNA displayed significantly enhanced mucus penetration, attributable to the charge screen effect of HA–DA and the bioadhesive nature of the grafting DA. After transmucosal delivery, the nanosystem could target diseased macrophages via CD44-mediated internalization and rapidly escape from endo/lysosomes through the proton sponge effect, resulting in effective TNF-α regulation. Meanwhile, DA modification endowed the coating material with robust antioxidative capability to scavenge a broad spectrum of reactive oxygen/nitrogen species (RONS), which protected the lung tissue from oxidative damage and synergized with anti-TNF-α to inhibit a cytokine storm. As a result, a remarkable amelioration of ALI was achieved in a lipopolysaccharide (LPS)-stimulated mice model. This study provides a multifunctional coating material to facilitate pulmonary drug delivery for the treatment of lung diseases.

研究领域: 药学 · 纳米技术 · 生物医学工程 · 肺科学 · 治疗学
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