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Senile osteoporosis is associated with the accumulation of reactive oxygen species, senescence of osteoprogenitor cells, and macrophage inflammation. Although Prussian blue nanozymes have antioxidant potential, they suffer from poor targeting and short circulation time. We prepared citrate-modified Prussian blue nanozymes camouflaged with macrophage membranes. The membrane coating extended their blood half-life by 1.47 times and increased bone tissue accumulation by 3.09 times. In vitro, these nanozymes cleared superoxide anions and hydrogen peroxide, reduced osteoprogenitor cell senescence, promoted M1-to-M2 polarization of macrophages, and decreased RANKL and TNF-α secretion. In vivo, they significantly increased bone volume fraction, alleviated bone loss, and improved movement and mood disorders. Mechanistically, they intervene in the ROS-senescence-inflammation axis and balance bone remodeling.
This work combines the catalytic activity of nanozymes with biomimetic cell membrane targeting, solving the problem of low bone tissue delivery efficiency of Prussian blue, and clarifies its mechanism of action through the senescence-inflammation axis. Future improvements could optimize membrane sources or surface modifications to enhance targeting accuracy for different bone sites. This strategy could be extended to other bone diseases related to oxidative stress and cell senescence, such as glucocorticoid-induced osteoporosis or delayed fracture healing. The imaging properties of Prussian blue help track its distribution in the body. Long-term accumulation and safety of repeated dosing still need further evaluation, but this biomimetic design offers a translatable therapeutic approach for age-related bone diseases.
Reference:
DOI:10.1186/s12951-026-04771-x
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