Sea cucumber-inspired dual-responsive black phosphorus/amorphous calcium-based bone-targeting nanoplatform for synergistic therapy of osteoporosis.

The core pathological mechanism of osteoporosis (OP) resides in the imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Furthermore, the accumulation of reactive oxygen species (ROS) and pro-inflammatory factors in bone tissue induces disorders in the immune microenvironment, which substantially elevates the risk of fracture. Inspired by the biological behaviors of sea cucumbers, we designed and constructed a bone-targeting platform (BA@PDA-PA) based on black phosphorus (BP) and amorphous calcium carbonate (ACC). This platform enables precise targeted therapy for diseased bone tissue while improving drug bioavailability. Upon reaching the target site, BA@PDA-PA can respond to the acidic microenvironment of OP lesions, and then release BP and calcium ions (Ca2+) on demand. Specifically, BP efficiently scavenges local excessive ROS and improves the immune microenvironment. Meanwhile, the Ca2+ released from ACC degradation, along with the low phosphorus oxides derived from BP breakdown, work together to promote osteoblast proliferation and differentiation while inhibiting osteoclast activity. This establishes a synergistic therapeutic mechanism involving "targeted delivery, microenvironment regulation, and bone metabolism remodeling." In vivo experimental results demonstrate that this platform significantly improves the pathological bone microstructure of OP mice, thereby providing a promising therapeutic strategy for OP treatment.