Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice.

Autor: García-García P; Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, 38206, La Laguna, Spain.; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38320, La Laguna, Spain., Reyes R; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38320, La Laguna, Spain.; Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, 38206, La Laguna, Spain., García-Sánchez D; Department of Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVAL, 39012, Santander, Spain., Pérez-Campo FM; Department of Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVAL, 39012, Santander, Spain., Rodríguez-Rey JC; Department of Molecular Biology, Faculty of Medicine, University of Cantabria-IDIVAL, 39012, Santander, Spain., Évora C; Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, 38206, La Laguna, Spain.; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38320, La Laguna, Spain., Díaz-Rodríguez P; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38320, La Laguna, Spain. patricia.diaz.rodriguez@usc.es.; Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma Group (GI-1645), Facultad de Farmacia, Instituto de Materiales (iMATUS) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain. patricia.diaz.rodriguez@usc.es., Delgado A; Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, 38206, La Laguna, Spain. adelgado@ull.edu.es.; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38320, La Laguna, Spain. adelgado@ull.edu.es.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2022 Oct 29; Vol. 20 (1), pp. 462. Date of Electronic Publication: 2022 Oct 29.
DOI: 10.1186/s12951-022-01674-5
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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