A bone-homing DNA tetrahedral framework nucleic acids nanodevice orchestrates osteogenic regeneration to rescue postmenopausal osteoporosis

1.Background
PMOP is linked to an imbalanced bone microenvironment and chronic inflammation, with rapid deterioration of bone microstructure. Current osteogenic molecules face delivery limits: low bioavailability, fast systemic clearance, uneven distribution, and high doses that raise extra-skeletal toxicity. A programmable, actively bone-targeted nanoplatform is needed to bring active molecules near osteogenic cells and reduce nonspecific distribution.

2.Research Innovation
tFNA is conjugated with the osteogenic-targeting peptide SDSSD and loaded with Gen to form tFNA-SDSSD/Gen. SDSSD binds periostin on the osteoblast surface, enhancing bone enrichment and cell uptake. The device acts as a molecular switch, co-activating PI3K/AKT and MAPK to reverse inflammation-driven osteogenic arrest. Targeting shifts from passive distribution to active bone and osteoblast recognition.

3.Material Study
PAGE and capillary electrophoresis confirmed assembly; the device remained stable in serum for 12 h. DLS showed size increasing from about 22 nm to 32 nm; TEM/AFM revealed a rigid tetrahedron of about 20 nm. Drug loading reached saturation at 1:40, and cellular uptake reached 99.3%. In vivo imaging and cleared 3D imaging showed the device entering cortical bone along vessels and enriching in trabeculae and marrow; SDSSD improved bone-targeted retention.

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#BoneTargetedDelivery #DNAFrameworkNucleicAcid #OsteoblastTargeting #PostmenopausalBoneLoss #ResearchUpdate

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