The Institute for Biomedical Engineering & Nano Science, School of Medicine, Shanghai Skin Disease Hospital of Tongji University, Tongji University, Shanghai, 200092, China.
Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China.
J Nanobiotechnology. 2024 Aug 14;22(1):489. doi: 10.1186/s12951-024-02731-x.
Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.
巨噬细胞在糖尿病溃疡的愈合中起着关键作用。持续升高的血糖水平会损害巨噬细胞中的胰岛素信号通路，导致功能失调的巨噬细胞难以从促炎（M1）状态向修复（M2）状态转变。因此，通过胰岛素通路调节巨噬细胞炎症反应有望成为糖尿病溃疡的治疗方法。此外，生物膜的存在阻碍了药物渗透，由此产生的免疫抑制微环境加剧了促炎 M1 巨噬细胞的持续浸润。因此，我们设计了一系列负载自组装纳米颗粒的可溶解微针（表示为 NPF@MN），可以递送 NPF 纳米颗粒、具有降血糖和胰岛素样作用的酸敏感 NPF 释放原儿茶醛（PA），调节巨噬细胞向抗炎 M2 表型极化。此外，本研究通过 RNA-seq 和 GSEA 分析，广泛研究了 NPF@MN 通过激活胰岛素信号通路加速糖尿病溃疡愈合的机制。结果表明，与通路相关的因子如 IR、IRS-1、IRS-2 和 SHC 的表达减少。我们的工作提出了一种针对糖尿病溃疡胰岛素通路的创新治疗方法，并强调了其在临床管理中的转化潜力。
