Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction
Abstract Osteosarcoma is a malignant bone cancer usually characterized by symptoms of bone loss due to pathologically enhanced osteoclast activity. Activated osteoclasts enhance bone resorption and promote osteosarcoma cell progression by secreting various cytokines. Intercepting the detrimental int...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412014 |
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| author | Lin Li Guangyu Rong Xin Gao Yiyun Cheng Zhengwang Sun Xiaopan Cai Jianru Xiao |
| author_facet | Lin Li Guangyu Rong Xin Gao Yiyun Cheng Zhengwang Sun Xiaopan Cai Jianru Xiao |
| author_sort | Lin Li |
| collection | DOAJ |
| description | Abstract Osteosarcoma is a malignant bone cancer usually characterized by symptoms of bone loss due to pathologically enhanced osteoclast activity. Activated osteoclasts enhance bone resorption and promote osteosarcoma cell progression by secreting various cytokines. Intercepting the detrimental interplay between osteoclasts and osteosarcoma cells is considered as an option for osteosarcoma treatment. Here, a bone‐targeted fluoropeptide nanoparticle that can inhibit the nuclear factor kappa B (NF‐κB) signaling in both osteoclasts and osteosarcoma to address the above issue is developed. The NF‐κB essential modulator binding domain (NBD) peptide is conjugated with a fluorous tag to improve its proteolytic stability and intracellular penetration. The NBD peptide is efficiently delivered into cells after fluorination to induce apoptosis of osteocarcoma cells, and inhibits osteoclasts differentiation. The fluorous‐tagged NBD peptide is further co‐assembled with an oligo (aspartic acid) terminated fluoropeptide to form bone‐targeted peptide nanoparticles for osteosarcoma treatment. The targeted nanoparticles efficiently inhibited tumor progression and osteosarcoma‐induced bone destruction in vivo. This co‐assembled fluoropeptide nanoplatform proposed in this study offers a promising approach for targeted and intracellular delivery of peptide therapeutics in the treatment of various diseases. |
| format | Article |
| id | doaj-art-437881b6804e469ba503438bbeb44735 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-437881b6804e469ba503438bbeb447352025-01-09T11:44:46ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202412014Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone DestructionLin Li0Guangyu Rong1Xin Gao2Yiyun Cheng3Zhengwang Sun4Xiaopan Cai5Jianru Xiao6Department of Orthopedics Oncology Changzheng Hospital Navy Medical University Shanghai 200003 ChinaDepartment of Ophthalmology and Vision Science Shanghai Eye, Ear, Nose and Throat Hospital Fudan University Shanghai 200030 ChinaDepartment of Orthopedics Oncology Changzheng Hospital Navy Medical University Shanghai 200003 ChinaShanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory Biology School of Life Sciences East China Normal University Shanghai 200241 ChinaDepartment of Musculoskeletal Oncology Fudan University Shanghai Cancer Center Shanghai 200032 ChinaDepartment of Orthopedics Oncology Changzheng Hospital Navy Medical University Shanghai 200003 ChinaDepartment of Orthopedics Oncology Changzheng Hospital Navy Medical University Shanghai 200003 ChinaAbstract Osteosarcoma is a malignant bone cancer usually characterized by symptoms of bone loss due to pathologically enhanced osteoclast activity. Activated osteoclasts enhance bone resorption and promote osteosarcoma cell progression by secreting various cytokines. Intercepting the detrimental interplay between osteoclasts and osteosarcoma cells is considered as an option for osteosarcoma treatment. Here, a bone‐targeted fluoropeptide nanoparticle that can inhibit the nuclear factor kappa B (NF‐κB) signaling in both osteoclasts and osteosarcoma to address the above issue is developed. The NF‐κB essential modulator binding domain (NBD) peptide is conjugated with a fluorous tag to improve its proteolytic stability and intracellular penetration. The NBD peptide is efficiently delivered into cells after fluorination to induce apoptosis of osteocarcoma cells, and inhibits osteoclasts differentiation. The fluorous‐tagged NBD peptide is further co‐assembled with an oligo (aspartic acid) terminated fluoropeptide to form bone‐targeted peptide nanoparticles for osteosarcoma treatment. The targeted nanoparticles efficiently inhibited tumor progression and osteosarcoma‐induced bone destruction in vivo. This co‐assembled fluoropeptide nanoplatform proposed in this study offers a promising approach for targeted and intracellular delivery of peptide therapeutics in the treatment of various diseases.https://doi.org/10.1002/advs.202412014fluorinationfluoropeptideintracellular peptide deliveryosteosarcomatargeted nanoparticles |
| spellingShingle | Lin Li Guangyu Rong Xin Gao Yiyun Cheng Zhengwang Sun Xiaopan Cai Jianru Xiao Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction Advanced Science fluorination fluoropeptide intracellular peptide delivery osteosarcoma targeted nanoparticles |
| title | Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction |
| title_full | Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction |
| title_fullStr | Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction |
| title_full_unstemmed | Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction |
| title_short | Bone‐Targeted Fluoropeptide Nanoparticle Inhibits NF‐κB Signaling to Treat Osteosarcoma and Tumor‐Induced Bone Destruction |
| title_sort | bone targeted fluoropeptide nanoparticle inhibits nf κb signaling to treat osteosarcoma and tumor induced bone destruction |
| topic | fluorination fluoropeptide intracellular peptide delivery osteosarcoma targeted nanoparticles |
| url | https://doi.org/10.1002/advs.202412014 |
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