Details

Autor(en) / Beteiligte

• Seong, Semun
• Vijayan, Veena
• Kim, Jung Ha
• Kim, Kabsun
• Kim, Inyoung
• Cherukula, Kondareddy
• Park, In-Kyu
• Kim, Nacksung

Titel

Nano-formulations for bone-specific delivery of siRNA for silencing-induced regulation of bone formation and resorption to maximize therapeutic potential for bone-related diseases

Ist Teil von

• Biomaterials science, 2023-03, Vol.11 (7), p.2581-2589

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• CrkII, a member of the adaptor protein family, is known to participate in bone homeostasis via the regulation of osteoclasts and osteoblasts. Therefore, silencing CrkII would beneficially impact the bone microenvironment. In this study, CrkII siRNA encapsulated by a bone-targeting peptide (AspSerSer) 6 -liposome was evaluated for its therapeutic applications using a receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model. (AspSerSer) 6 -liposome- siCrkII maintained its gene-silencing ability in both osteoclasts and osteoblasts in vitro and significantly reduced osteoclast formation while increasing osteoblast differentiation in vitro . Fluorescence image analyses showed that the (AspSerSer) 6 -liposome- siCrkII was present largely in bone, where it remained present for up to 24 hours and was cleared by 48 hours, even when systemically administrated. Importantly, microcomputed-tomography revealed that bone loss induced by RANKL administration was recovered by systemic administration of (AspSerSer) 6 -liposome- siCrkII . Collectively, the findings of this study suggest that (AspSerSer) 6 -liposome- siCrkII is a promising therapeutic strategy for the development of treatments for bone diseases, as it overcomes the adverse effects derived from ubiquitous expression via bone-specific delivery of siRNA. Nano-formulated CrkII siRNA improves bone microenvironment via simultaneous regulation of the formation and function of both osteoclasts and osteoblasts.