Multifunctional Alendronate-PEI Carbon Dots for the Treatment of Bone-Destructive Diseases via Bidirectional Regulation of Osteoblast-Osteoclast Function

Bone damage results from the imbalance of bone homeostasis maintained by osteoblast-regulated bone formation and osteoclast-mediated bone resorption. Conventional drug therapy and gene therapy may not optimally regulate the bone remodeling process due to the unitary pharmacological mechanism of drug and the safety and targeting of gene vectors. In the present study, multifunctional fluorescent alendronate-polyethyleneimine carbon dots (Alen-PEI CDs) are innovatively synthesized, which have excellent biocompatibility, selective bone targeting, gene carrying capacity, and anti-bone absorption effect. As gene vectors, bone morphogenic protein 2 (BMP2) gene-loaded Alen-PEI CDs greatly enhance osteoblast differentiation and bone regeneration. Notably, Alen-PEI CDs are found to directly inhibit the formation and function of osteoclasts, effectively attenuating the LPS-induced skull osteolysis in mice. Furthermore, their cumulative toxicity is lower than that of Alen, indicating their potential as an anti-bone resorptive nanodrug. These results show that the bone-targeting Alen-PEI CDs significantly reverse the imbalance of bone homeostasis through a dual-directional mechanism-directly suppressing bone resorption and indirectly inducing bone formation by transfection of osteogenic therapeutic genes. Overall, the study expands the application for carbon dots in biomedicine, providing new insights for the further development of novel selectively targeted multifunctional nanodrugs for the treatment of bone-destructive diseases.