Microenvironment-responsive nanocarriers for targeted bone disease therapy

Nanomedicines with controlled drug release have received increasing attention as an advanced therapeutic strategy for bone diseases. To traverse biological barriers towards pathological site of bone and endow drug release with spatial, temporal and dose controllability, the design of nanocarriers based on bone microenvironment and their pathological changes during diseases is an attractive idea. Distinguishable biological, physical and chemical features of the bone pathological microenvironment can be exploited to develop targeted and stimuli-responsive nanocarriers thus maximizing the effective enrichment of drugs in the pathological microenvironment. Herein, we present a review of bone targeting strategies based on the characteristics of the bone microenvironment, their pathological changes during bone diseases and corresponding strategies for the construction of stimuli-responsive nanocarriers. The available stimuli in the context of bone disease, design principles of stimuli-responsive delivery systems and recent advances in their application for bone therapy were highlighted. Thereby, the emerging new concept, that is, the bone microenvironment-responsive drug delivery system, was systematically illustrated. Furthermore, the challenges and future prospects of such smart drug delivery systems for bone therapy applications are discussed.