Osteosarcoma, occurring most frequently in children, teens, and young adults, is a lethal bone cancer with a high incidence of distant metastases and drug resistance. Developing a therapeutic platform that integrates targeting, curing and imaging is highly desirable for enhanced osteosarcoma therapy, yet quite challenging. In this work, we demonstrate a novel biomineralization-inspired strategy for the synthesis of a fructose incorporated manganese phosphate (Fru-MnP) nanoplatform for tumour targeting, drug-free therapy, and MRI imaging. Benefitting from the glucose transporter 5 (GLUT5)-mediated endocytosis, our Fru-MnP nanoplatform produces a high level of reactive oxygen species (ROS) via the Mn2+-driven Fenton reaction within osteosarcoma cells, leading to efficient cancer cell killing due to caspase-mediated apoptosis. By virtue of the T1 signal enhancement of Mn2+, our Fru-MnP nanoplatform also acts as an effective tumour-specific MRI contrast agent, realizing the MRI-monitored chemodynamic therapy. The proposed synergistic therapeutic platform opens new possibilities for high efficacy therapy for osteosarcoma.