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.

CrkII, a member of the adaptor protein family, is known to participate in bone homeostasis the regulation of osteoclasts and osteoblasts. Therefore, silencing would beneficially impact the bone microenvironment. In this study, siRNA encapsulated by a bone-targeting peptide (AspSerSer)-liposome was evaluated for its therapeutic applications using a receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model. (AspSerSer)-liposome- maintained its gene-silencing ability in both osteoclasts and osteoblasts and significantly reduced osteoclast formation while increasing osteoblast differentiation . Fluorescence image analyses showed that the (AspSerSer)-liposome- 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)-liposome-. Collectively, the findings of this study suggest that (AspSerSer)-liposome- is a promising therapeutic strategy for the development of treatments for bone diseases, as it overcomes the adverse effects derived from ubiquitous expression bone-specific delivery of siRNA.