Bone imaging using ferritin nanoparticles genetically modified with peptides Moonil Kim Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahang-ro, Yuseong-gu, Daejeon 34141, South Korea The balance between osteoblast and osteoclast activity is essential for maintaining bone homeostasis, which is crucial for supporting and protecting various organs and the body's structure. When there is an imbalance, it can lead to skeletal diseases such as osteoporosis, osteopetrosis, and Paget's disease. Although synthetic nanomaterials have been developed for bone imaging and therapy, they have limitations such as heterogeneity and random orientation, leading to low efficiency. In this study, bone-targeting ferritin nanoparticles were synthesized for bone imaging. Ferritin, a globular protein composed of 24 subunits, was used as a carrier molecule. Bone-targeting peptides that specifically bind to osteoblasts and hydroxyapatite were genetically fused to the heavy subunit of human ferritin in a way that allowed the peptides to face outwards. The nanoparticles were conjugated with fluorescent dyes to assess their binding ability for osteoblast imaging and a hydroxyapatite binding assay, which showed specific binding with osteoblasts and hydroxyapatite. In vivo analysis demonstrated a specific fluorescent signal from the lower limb, indicating a highly selective affinity of the modified nanoparticles for bone tissue. These promising results suggest that this nanoscale targeting system may be used in future clinical applications for bone disease therapy. References 1. Sun, W.; Meednu, N.; Rosenberg, A.; Rangel-Moreno, J.; Wang, V.; Glanzman, J.; Owen, T.; Zhou, X.; Zhang, H.; Boyce, B.F.; et al. B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation.Nat. Commun. 2018 ,9, 5127. 2. Wang, M.; Xia, F.; Wei, Y.; Wei, X. Molecular mechanisms and clinical management of cancer bone metastasis.Bone Res. 2020 ,8, 30. 3. Luther, D.C.; Huang, R.; Jeon, T.; Zhang, X.; Lee, Y.W.; Nagaraj, H.; Rotello, V.M. Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles.Adv. Drug Deliv. Rev. 2020 ,156, 188–213. 4. Khoshnejad, M.; Parhiz, H.; Shuvaev, V.V.; Dmochowski, I.J.; Muzykantov, V.R. Ferritin-based drug delivery systems: Hybrid nanocarriers for vascular immunotargeting.J. Control. Release 2018 ,282, 13–24. 5. He, J.; Fan, K.; Yan, X. Ferritin drug carrier (FDC) for tumor targeting therapy.J. Control. Release 2019 ,311–312, 288–300.
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