Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging
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,...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4854 |
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| author | Jong-Won Kim Kyung-Kwan Lee Kyoung-Woo Park Moonil Kim Chang-Soo Lee |
| author_facet | Jong-Won Kim Kyung-Kwan Lee Kyoung-Woo Park Moonil Kim Chang-Soo Lee |
| author_sort | Jong-Won Kim |
| collection | DOAJ |
| description | 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’s 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. |
| first_indexed | 2024-03-10T11:43:14Z |
| format | Article |
| id | doaj.art-41b5d07386d542f3bea2510681f7a947 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:43:14Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-41b5d07386d542f3bea2510681f7a9472023-11-21T18:18:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229485410.3390/ijms22094854Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone ImagingJong-Won Kim0Kyung-Kwan Lee1Kyoung-Woo Park2Moonil Kim3Chang-Soo Lee4Bionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, KoreaBionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, KoreaBionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, KoreaBionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, KoreaBionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, KoreaBone 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’s 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.https://www.mdpi.com/1422-0067/22/9/4854bone-targeting peptidesferritin nanoparticlesosteoblastshydroxyapatitebioimaging |
| spellingShingle | Jong-Won Kim Kyung-Kwan Lee Kyoung-Woo Park Moonil Kim Chang-Soo Lee Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging International Journal of Molecular Sciences bone-targeting peptides ferritin nanoparticles osteoblasts hydroxyapatite bioimaging |
| title | Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging |
| title_full | Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging |
| title_fullStr | Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging |
| title_full_unstemmed | Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging |
| title_short | Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging |
| title_sort | genetically modified ferritin nanoparticles with bone targeting peptides for bone imaging |
| topic | bone-targeting peptides ferritin nanoparticles osteoblasts hydroxyapatite bioimaging |
| url | https://www.mdpi.com/1422-0067/22/9/4854 |
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