{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:26:02Z","timestamp":1779909962022,"version":"3.53.1"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["QLT-CRC-18-01-ETRI"],"award-info":[{"award-number":["QLT-CRC-18-01-ETRI"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1A2C1084687"],"award-info":[{"award-number":["NRF-2019R1A2C1084687"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003715","name":"Korea Research Institute of Bioscience and Biotechnology","doi-asserted-by":"publisher","award":["KGM5472113"],"award-info":[{"award-number":["KGM5472113"]}],"id":[{"id":"10.13039\/501100003715","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bone homeostasis plays a major role in supporting and protecting various organs as well as a body structure by maintaining the balance of activities of the osteoblasts and osteoclasts. Unbalanced differentiation and functions of these cells result in various skeletal diseases, such as osteoporosis, osteopetrosis, and Paget\u2019s disease. Although various synthetic nanomaterials have been developed for bone imaging and therapy through the chemical conjugation, they are associated with serious drawbacks, including heterogeneity and random orientation, in turn resulting in low efficiency. Here, we report the synthesis of bone-targeting ferritin nanoparticles for bone imaging. Ferritin, which is a globular protein composed of 24 subunits, was employed as a carrier molecule. Bone-targeting peptides that have been reported to specifically bind to osteoblast and hydroxyapatite were genetically fused to the N-terminus of the heavy subunit of human ferritin in such a way that the peptides faced outwards. Ferritin nanoparticles with fused bone-targeting peptides were also conjugated with fluorescent dyes to assess their binding ability using osteoblast imaging and a hydroxyapatite binding assay; the results showed their specific binding with osteoblasts and hydroxyapatite. Using in vivo analysis, a specific fluorescent signal from the lower limb was observed, demonstrating a highly selective affinity of the modified nanoparticles for the bone tissue. These promising results indicate a specific binding ability of the nanoscale targeting system to the bone tissue, which might potentially be used for bone disease therapy in future clinical applications.<\/jats:p>","DOI":"10.3390\/ijms22094854","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T11:06:01Z","timestamp":1620212761000},"page":"4854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging"],"prefix":"10.3390","volume":"22","author":[{"given":"Jong-Won","family":"Kim","sequence":"first","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience &amp; Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Kwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience &amp; Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience &amp; Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Biotechnology, University of Science &amp; Technology (UST), Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moonil","family":"Kim","sequence":"additional","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience &amp; Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Biotechnology, University of Science &amp; Technology (UST), Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4965-5070","authenticated-orcid":false,"given":"Chang-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Bionanotechnology Research Center, Korea Research Institute of Bioscience &amp; Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Biotechnology, University of Science &amp; Technology (UST), Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25103","DOI":"10.1074\/jbc.R109.041087","article-title":"Cellular and molecular mechanisms of bone remodeling","volume":"285","author":"Raggatt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/bonekey.2013.215","article-title":"Coupling the activities of bone formation and resorption: A multitude of signals within the basic multicellular unit","volume":"3","author":"Sims","year":"2014","journal-title":"Bonekey Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jconrel.2011.10.001","article-title":"Bone targeting for the treatment of osteoporosis","volume":"161","author":"Luhmann","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/S0140-6736(10)62349-5","article-title":"Osteoporosis: Now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"46","DOI":"10.5152\/eurjrheum.2016.048","article-title":"An overview and management of osteoporosis","volume":"4","author":"Sozen","year":"2017","journal-title":"Eur. J. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"832127","DOI":"10.1155\/2015\/832127","article-title":"Bone Loss Triggered by the Cytokine Network in Inflammatory Autoimmune Diseases","volume":"2015","author":"Amarasekara","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5127","DOI":"10.1038\/s41467-018-07626-8","article-title":"B cells inhibit bone formation in rheumatoid arthritis by suppressing osteoblast differentiation","volume":"9","author":"Sun","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/sj.cr.7290266","article-title":"Mechanisms of cancer metastasis to the bone","volume":"15","author":"Yin","year":"2005","journal-title":"Cell Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41413-020-00105-1","article-title":"Molecular mechanisms and clinical management of cancer bone metastasis","volume":"8","author":"Wang","year":"2020","journal-title":"Bone Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.amjmed.2012.06.023","article-title":"Bisphosphonate therapy for osteoporosis: Benefits, risks, and drug holiday","volume":"126","author":"McClung","year":"2013","journal-title":"Am. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6620","DOI":"10.1039\/c3cs60036j","article-title":"Conjugated polymer nanoparticles: Preparation, properties, functionalization and biological applications","volume":"42","author":"Feng","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fphar.2015.00286","article-title":"Advances and Challenges of Liposome Assisted Drug Delivery","volume":"6","author":"Sercombe","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.addr.2020.06.020","article-title":"Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles","volume":"156","author":"Luther","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.3389\/fphar.2018.01401","article-title":"Carbon-Based Nanomaterials for Biomedical Applications: A Recent Study","volume":"9","author":"Maiti","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jconrel.2016.04.025","article-title":"Bone-targeted delivery of nanodiamond-based drug carriers conjugated with alendronate for potential osteoporosis treatment","volume":"232","author":"Ryu","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1039\/C7CS00877E","article-title":"Peptide and protein nanoparticle conjugates: Versatile platforms for biomedical applications","volume":"47","author":"Spicer","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.nantod.2010.05.003","article-title":"Functionalisation of nanoparticles for biomedical applications","volume":"5","author":"Thanh","year":"2010","journal-title":"Nano Today"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.bi.56.070187.001445","article-title":"Ferritin: Structure, gene regulation, and cellular function in animals, plants, and microorganisms","volume":"56","author":"Theil","year":"1987","journal-title":"Annu. Rev. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s11705-017-1620-8","article-title":"Functional ferritin nanoparticles for biomedical applications","volume":"11","author":"Wang","year":"2017","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1021\/nl104141g","article-title":"Chimeric ferritin nanocages for multiple function loading and multimodal imaging","volume":"11","author":"Lin","year":"2011","journal-title":"Nano Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1039\/C1NR11132A","article-title":"Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells","volume":"4","author":"Li","year":"2012","journal-title":"Nanoscale"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jconrel.2018.02.042","article-title":"Ferritin-based drug delivery systems: Hybrid nanocarriers for vascular immunotargeting","volume":"282","author":"Khoshnejad","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1016\/j.vaccine.2020.06.063","article-title":"A ferritin nanoparticle vaccine for foot-and-mouth disease virus elicited partial protection in mice","volume":"38","author":"Chen","year":"2020","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.aca.2017.07.060","article-title":"Genetically functionalized ferritin nanoparticles with a high-affinity protein binder for immunoassay and imaging","volume":"988","author":"Kim","year":"2017","journal-title":"Anal. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1039\/C8BM01340C","article-title":"Peptide ligand-mediated targeted drug delivery of nanomedicines","volume":"7","author":"Jiang","year":"2019","journal-title":"Biomater. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jconrel.2019.11.005","article-title":"Non-immunogenic, low-toxicity and effective glioma targeting MTI-31 liposomes","volume":"316","author":"Wang","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1021\/acs.molpharmaceut.7b00520","article-title":"Targeted Cancer Therapy Using Fusion Protein of TNFalpha and Tumor-Associated Fibronectin-Specific Aptide","volume":"14","author":"Jeon","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5759","DOI":"10.1021\/acsnano.5b07828","article-title":"Osteoblast-Targeting-Peptide Modified Nanoparticle for siRNA\/microRNA Delivery","volume":"10","author":"Sun","year":"2016","journal-title":"ACS Nano"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1359\/jbmr.2000.15.5.936","article-title":"Selective drug delivery system to bone: Small peptide (Asp)6 conjugation","volume":"15","author":"Kasugai","year":"2000","journal-title":"J. Bone Miner. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/jcb.20115","article-title":"Expression and function of periostin-isoforms in bone","volume":"92","author":"Litvin","year":"2004","journal-title":"J. Cell Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1021\/bm070121s","article-title":"Synthesis and in vitro hydroxyapatite binding of peptides conjugated to calcium-binding moieties","volume":"8","author":"Murphy","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3536","DOI":"10.1016\/j.actbio.2011.06.019","article-title":"alpha-Tricalcium phosphate: Synthesis, properties and biomedical applications","volume":"7","author":"Carrodeguas","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1002\/anie.201006757","article-title":"Hybrid ferritin nanoparticles as activatable probes for tumor imaging","volume":"50","author":"Lin","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.jconrel.2019.09.002","article-title":"Ferritin drug carrier (FDC) for tumor targeting therapy","volume":"311\u2013312","author":"He","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis","volume":"344","author":"Neer","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrendo.2011.108","article-title":"Parathyroid hormone analogues in the treatment of osteoporosis","volume":"7","author":"Kraenzlin","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bios.2018.01.018","article-title":"Fast and sensitive near-infrared fluorescent probes for ALP detection and 3d printed calcium phosphate scaffold imaging in vivo","volume":"105","author":"Park","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1002\/smll.201200066","article-title":"Epidermal growth factor-ferritin H-chain protein nanoparticles for tumor active targeting","volume":"8","author":"Li","year":"2012","journal-title":"Small"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nchembio.1163","article-title":"Re-engineering protein interfaces yields copper-inducible ferritin cage assembly","volume":"9","author":"Huard","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1021\/bm200026v","article-title":"pH-dependent structures of ferritin and apoferritin in solution: Disassembly and reassembly","volume":"12","author":"Kim","year":"2011","journal-title":"Biomacromolecules"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4854\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:56:58Z","timestamp":1760162218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,3]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094854"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094854","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,3]]}}}