2. Academic Validation
  3. Chemotactic recruitment of genetically engineered cell membrane-camouflaged metal-organic framework nanoparticles for ischemic osteonecrosis treatment

Chemotactic recruitment of genetically engineered cell membrane-camouflaged metal-organic framework nanoparticles for ischemic osteonecrosis treatment

  • Acta Biomater. 2024 Jul 17:S1742-7061(24)00395-7. doi: 10.1016/j.actbio.2024.07.024.
Hongyi Jiang 1,  Weijie Xia 1,  Tian Xia 2,  Liting Jiang 1,  Jiachen Yu 1,  Xinyi Zhu 1,  Chihao Lin 1,  Chao Lou 1,  Weidan Wang 1,  Yingqian Chai 2,  Renwen Wan 3,  Jilong Wang 4,  Xinghe Xue 5,  Xiaoyun Pan 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, People's Republic of China.
  • 3 Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.
  • 4 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, People's Republic of China. Electronic address: wangjilong@ucas.ac.cn.
  • 5 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: 213205@wzhealth.com.
  • 6 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second Clinical School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: xiaoyunpan@126.com.
PMID: 39029641 DOI: 10.1016/j.actbio.2024.07.024
Abstract

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.

Keywords

CXCR4; Genetically engineered cell membrane; Ischemic osteonecrosis; Metal−organic framework; miRNA delivery.

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