Regenerating aged bone marrow via a nitric oxide nanopump

Resident leptin-receptor-expressing (LepR+) cells senescence in the aged bone marrow impairs the regenerative capacity of osteo- and other lineages of cells. In this study, a LepR+ cell-targeting nitric oxide (NO) nanopump with in vivo self-controlled turn-on ability was constructed to rejuvenate the LepR+ cells in the aged bone marrow. The nanopump co-entrapped hydrophobic chemiluminescence substrate and NO donor into the matrix of amphiphilic polymer through a nanoprecipitation process. The chemiluminescence substrate in the NO nanopump automatically reacts with the accumulated H2O2 in the aged bone marrow and then directly transfers the chemical energy to the NO donor to induce in situ NO release. The NO produced in situ within the aged bone marrow triggered the regeneration of the osteoblastic and the other niches in vivo through activating the glycolysis signaling in the senescent LepR+ cells. Conclusively, the constructed NO nanopump is a promising tool to counter aging-induced bone marrow disorders. LepR+ cells senescence is a driver of aging-induced bone marrow homeostasis collapse. Here, Li et al. report a LepR+ cell-targeting nitric oxide (NO) nanopump for rejuvenation of senescent LepR+ cells via activation of glycolysis signaling to reestablish homeostasis of the aged bone marrow.