Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The first Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China; Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen 361102, China.
J Control Release. 2020 Apr 10;320:304-313. doi: 10.1016/j.jconrel.2020.01.054. Epub 2020 Jan 28.
Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Although the progress made with current clinical use of biologic disease-modifying antirheumatic drugs (bioDMARDs), the response rate of RA treatment remains ungratified, primarily due to intricacy interactions of multiple inflammatory cytokines and the awkward drug delivery. Thus, it is of great importance to neutralize cytokines and actively deliver therapeutic agents to RA joints for the purpose of promoting in situ activity. Herein, we proposed and validated a nanoparticle-based broad-spectrum anti-inflammatory strategy for RA management by fusing TRAIL-anchored cell membranes onto drug-loaded polymeric cores (TU-NPs), which makes them ideal decoys of inflamed macrophage-targeted biological molecules. Upon intravenous injection of TU-NPs into collagen-induced arthritic mice, the fluorescence/photoacoustic dual-modal imaging revealed higher accumulations and longer retention of TU-NPs in inflamed joints. In vivo therapeutic evaluations suggested that these nanoparticles could neutralize cytokines, suppress synovial inflammation, and provide strong chondroprotection against joint damage by targeting and deep penetration into the inflamed tissues. Overall, our work provides a novel strategy to treat RA with a strong potential for clinical translation.
类风湿性关节炎（RA）是最常见的慢性自身免疫性疾病之一。尽管目前临床上使用生物疾病修饰抗风湿药物（bioDMARDs）取得了进展，但 RA 治疗的反应率仍不尽如人意，主要是由于多种炎症细胞因子的复杂相互作用和药物传递的困难。因此，中和细胞因子并将治疗剂主动递送到 RA 关节以促进原位活性非常重要。在这里，我们通过将 TRAIL 锚定的细胞膜融合到载药聚合物核上（TU-NPs），提出并验证了一种基于纳米颗粒的治疗 RA 的广谱抗炎策略，使其成为炎症巨噬细胞靶向生物分子的理想诱饵。将 TU-NPs 静脉注射到胶原诱导性关节炎小鼠中后，荧光/光声双模成像显示 TU-NPs 在炎症关节中的积累更高，保留时间更长。体内治疗评估表明，这些纳米颗粒可以通过靶向和深入渗透到炎症组织中来中和细胞因子、抑制滑膜炎症，并提供对关节损伤的强烈软骨保护作用。总的来说，我们的工作为治疗 RA 提供了一种具有很强临床转化潜力的新策略。
