Osteosarcoma is the most common malignant tumor in the skeletal system with high mortality. Phytic acid (PA) is a natural compound extracted from plant seeds, which shows certain antitumor activity and good bone targeting ability. To develop a novel theranostics for magnetic resonance imaging (MRI) and targeting therapy of osteosarcoma, we employed PA to modify manganese dioxide nanoparticles (MnO
2
@PA NPs) for osteosarcoma treatment. The MnO
2
NPs oligomer was formed by PA modification with uniformed size distribution and negative zeta potential. Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis demonstrated that PA has been successfully modified on MnO
2
NPs, and the structure of MnO
2
@PA NPs is amorphous.
In vitro
experiments demonstrated that MnO
2
@PA NPs oligomer can be efficiently internalized by tumor cell, and the internalized NPs can react with H
2
O
2
under acid microenvironment to produce Mn
2+
and O
2
.
In vivo
experiments demonstrated that MnO
2
@PA NPs oligomer can passively accumulate in tumor tissue, and the accumulated NPs can produce Mn
2+
and O
2
for MRI and targeting therapy of osteosarcoma. In conclusion, we prepared a novel bone-targeting nano theranostics for MRI and therapy of osteosarcoma.