PDF(Pubmed)
Abstract：
Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.
摘要：
下背痛（LBP）是与椎间盘退变（IDD）密切相关的常见病，造成重大的社会经济负担。变性椎间盘的炎症激活涉及促炎细胞因子，失调的调节细胞因子，神经生长因子（NGF）水平升高，导致椎间盘进一步破坏和疼痛敏感。巨噬细胞极化与自噬密切相关。基于这些病理特征,开发了一种结构化的仿生纳米颗粒，该纳米颗粒涂有TrkA过表达的巨噬细胞膜（TMNP@SR），并带有雷帕霉素负载的介孔二氧化硅核。TMNP@SR像海绵一样吸附炎性细胞因子和NGF，并通过外部工程化细胞膜的同源靶向作用将自噬调节剂雷帕霉素（RAPA）递送到巨噬细胞中。通过调节自噬激活，TMNP@SR促进巨噬细胞的M1-M2转换，以避免变性椎间盘内炎症的持续激活，防止髓核细胞凋亡。此外,TMNP@SR缓解了机械和热痛觉过敏，降钙素基因相关肽（CGRP）和P物质（SP）在背根神经节中的表达降低，并下调大鼠IDD模型脊髓GFAP和c-FOS信号传导。总之,TMNP@SR自发抑制椎间盘炎症的加重，缓解椎间盘退变，减少感觉神经的进入，为椎间盘退变引起的LBP提供了一种有希望的治疗策略。
