趋化性
材料科学
基因工程
纳米颗粒
膜
纳米技术
生物医学工程
医学
化学
受体
生物化学
内科学
基因
作者
Hongyi Jiang,Weijie Xia,Tian Xia,Liting Jiang,Jiachen Yu,Xinyi Zhu,Chihao Lin,Chao Lou,Weidan Wang,Yingqian Chai,Renwen Wan,Jilong Wang,Xinghe Xue,Xiaoyun Pan
标识
DOI:10.1016/j.actbio.2024.07.024
摘要
Ischemic osteonecrosis, particularly glucocorticoid-induced osteonecrosis of the femoral head (GIONFH), is primarily due to the dysfunction of osteogenesis and angiogenesis. miRNA, as a therapeutic system with immense potential, plays a vital role in the treatment of various diseases. However, due to the unique microenvironmental structure of bone tissue, especially in the case of GIONFH, where there is a deficiency in the vascular system, it is challenging to effectively target and deliver to the ischemic osteonecrosis area. A drug delivery system assisted by genetically engineered cell membranes holds promise in addressing the challenge of targeted miRNA delivery. Herein, we leverage the potential of miR-21 in modulating osteogenesis and angiogenesis to design an innovative biomimetic nanoplatform system. First, we employed metal-organic frameworks (MOFs) as the core structure to load miR-21-m (miR-21-m@MOF). The nanoparticles were further coated with the membrane of bone marrow mesenchymal stem cells overexpressing CXCR4 (CM-miR-21-m@MOF), enhancing their ability to target ischemic bone areas via the CXCR4-SDF1 axis. These biomimetic nanocomposites possess both bone-targeting and ischemia-guiding capabilities, actively targeting GIONFH lesions to release miR-21-m into target cells, thereby silencing PTEN gene and activating the PI3K-AKT signaling pathway to regulate osteogenesis and angiogenesis. This innovative miRNA delivery system provides a promising therapeutic avenue for GIONFH and potentially other related ischemic bone diseases. STATEMENT OF SIGNIFICANCE: 1. CXCR4-Engineered Membranes Enhance Targeting for Ischemic Osteonecrosis. 2. miR-21-Based Gene Therapy for Regulating Osteogenesis and Angiogenesis. 3. Expanding the Use of Membrane-Cloaked MOF Nanoparticles.
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