Chemotactic Recruitment of Genetically Engineered Cell Membrane-Camouflaged Metal−Organic Framework Nanoparticles for Ischemic Osteonecrosis Treatment

趋化性 材料科学 基因工程 纳米颗粒 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
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:185: 410-428
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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