Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice
Abstract Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone formation, this pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1), antagonist of...
| 主要な著者: | , , , , , , , |
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| フォーマット: | 論文 |
| 言語: | English |
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BMC
2022-10-01
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| シリーズ: | Journal of Nanobiotechnology |
| 主題: | |
| オンライン･アクセス: | https://doi.org/10.1186/s12951-022-01674-5 |
| _version_ | 1828317093507891200 |
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| author | Patricia García-García Ricardo Reyes Daniel García-Sánchez Flor María Pérez-Campo José Carlos Rodríguez-Rey Carmen Évora Patricia Díaz-Rodríguez Araceli Delgado |
| author_facet | Patricia García-García Ricardo Reyes Daniel García-Sánchez Flor María Pérez-Campo José Carlos Rodríguez-Rey Carmen Évora Patricia Díaz-Rodríguez Araceli Delgado |
| author_sort | Patricia García-García |
| collection | DOAJ |
| description | Abstract Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone formation, this pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1), antagonist of the pathway. Thus, Sfrp-1 silencing therapies could be suitable for enhancing bone growth. However, the systemic stimulation of Wnt/β-catenin has been correlated with side effects. This work hypothesizes the administration of lipid-polymer NPs (LPNPs) functionalized with a MSC specific aptamer (Apt) and carrying a SFRP1 silencing GapmeR, could favor bone formation in OP with minimal undesired effects. Suitable SFRP1 GapmeR-loaded Apt-LPNPs (Apt-LPNPs-SFRP1) were administered in osteoporotic mice and their biodistribution, toxicity and bone induction capacity were evaluated. The aptamer functionalization of the NPs modified their biodistribution profile showing a four-fold increase in the bone accumulation and a ten-fold decrease in the hepatic accumulation compared to naked LPNPs. Moreover, the histological evaluation revealed evident changes in bone structure observing a more compact trabecular bone and a cortical bone thickness increase in the Apt-LPNPs-SFRP1 treated mice with no toxic effects. Therefore, these LPNPs showed suitable properties and biodistribution profiles leading to an enhancement on the bone density of osteoporotic mice. |
| first_indexed | 2024-04-13T17:23:19Z |
| format | Article |
| id | doaj.art-9981d1fd9fec4dba8f6f3a8b83d7775f |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T17:23:19Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-9981d1fd9fec4dba8f6f3a8b83d7775f2022-12-22T02:37:54ZengBMCJournal of Nanobiotechnology1477-31552022-10-0120111910.1186/s12951-022-01674-5Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic micePatricia García-García0Ricardo Reyes1Daniel García-Sánchez2Flor María Pérez-Campo3José Carlos Rodríguez-Rey4Carmen Évora5Patricia Díaz-Rodríguez6Araceli Delgado7Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La LagunaInstitute of Biomedical Technologies (ITB), Universidad de La LagunaDepartment of Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVALDepartment of Chemical Engineering and Pharmaceutical Technology, Universidad de La LagunaInstitute of Biomedical Technologies (ITB), Universidad de La LagunaDepartment of Chemical Engineering and Pharmaceutical Technology, Universidad de La LagunaAbstract Osteoporosis (OP) is characterized by a loss in bone mass and mineral density. The stimulation of the canonical Wnt/β-catenin pathway has been reported to promote bone formation, this pathway is controlled by several regulators as secreted frizzled-related protein-1 (Sfrp-1), antagonist of the pathway. Thus, Sfrp-1 silencing therapies could be suitable for enhancing bone growth. However, the systemic stimulation of Wnt/β-catenin has been correlated with side effects. This work hypothesizes the administration of lipid-polymer NPs (LPNPs) functionalized with a MSC specific aptamer (Apt) and carrying a SFRP1 silencing GapmeR, could favor bone formation in OP with minimal undesired effects. Suitable SFRP1 GapmeR-loaded Apt-LPNPs (Apt-LPNPs-SFRP1) were administered in osteoporotic mice and their biodistribution, toxicity and bone induction capacity were evaluated. The aptamer functionalization of the NPs modified their biodistribution profile showing a four-fold increase in the bone accumulation and a ten-fold decrease in the hepatic accumulation compared to naked LPNPs. Moreover, the histological evaluation revealed evident changes in bone structure observing a more compact trabecular bone and a cortical bone thickness increase in the Apt-LPNPs-SFRP1 treated mice with no toxic effects. Therefore, these LPNPs showed suitable properties and biodistribution profiles leading to an enhancement on the bone density of osteoporotic mice.https://doi.org/10.1186/s12951-022-01674-5Bone regenerationOsteoporosisGene therapyLipid-polymer hybrid nanoparticles |
| spellingShingle | Patricia García-García Ricardo Reyes Daniel García-Sánchez Flor María Pérez-Campo José Carlos Rodríguez-Rey Carmen Évora Patricia Díaz-Rodríguez Araceli Delgado Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice Journal of Nanobiotechnology Bone regeneration Osteoporosis Gene therapy Lipid-polymer hybrid nanoparticles |
| title | Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice |
| title_full | Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice |
| title_fullStr | Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice |
| title_full_unstemmed | Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice |
| title_short | Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice |
| title_sort | nanoparticle mediated selective sfrp 1 silencing enhances bone density in osteoporotic mice |
| topic | Bone regeneration Osteoporosis Gene therapy Lipid-polymer hybrid nanoparticles |
| url | https://doi.org/10.1186/s12951-022-01674-5 |
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