RT info:eu-repo/semantics/article
T1 Nanoparticle-mediated selective Sfrp-1 silencing enhances bone density in osteoporotic mice.
A1 Delgado Hernández, Araceli Rita
A1 García García, Patricia
A1 Reyes, Ricardo
A1 García Sánchez, Daniel
A1 Pérez Campo, Flor María
A1 Rodríguez Rey, José Carlos
A1 Évora, Carmen
A1 Díaz Rodríguez, Patricia
K1 Bone regeneration
K1 Osteoporosis
K1 Gene therapy
K1 Lipid‑polymer hybrid nanoparticles
AB 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.
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/36140
UL http://riull.ull.es/xmlui/handle/915/36140
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 19-dic-2024