The combination of chemotherapy and photothermal therapy not only improves the therapeutic effect but also limits the side effects of drugs. Herein, a multi-responsive dual-modality bone-targeted drug delivery vehicle for the treatment of osteosarcoma was designed by utilizing alendronate sodium as a bone-targeting ligand for the targeted delivery of doxorubicin (DOX) loaded polydopamine nanoparticles (PDA NPs) coated with γ-polyglutamic acid (APC@PDA/DOX NPs). The average size of spherical NPs was 140.0 nm with a zeta potential of -25.63 mV. The drug loading and encapsulation efficiency were 11.63 % and 96.44 %, respectively. The constructed NPs were responsive to acidic pH, redox conditions, and near-infrared light as the drug release rate of the system reached 70 %. Cell experiments showed that APC@PDA/DOX NPs significantly enhanced cytotoxicity in mouse K7M2 osteosarcoma cells due to PDA-induced hyperthermia and DOX-induced cytotoxicity. Compared with the free DOX solution, the area under the curve of APC@PDA/DOX NPs increased by 8.52 times, iterating the significantly prolonged circulation time of NPs in vivo that manifested in higher bioavailability. The biodistribution study showed that APC@PDA/DOX NPs enacted excellent bone targeting and tumor tissue localization. In general, APC@PDA/DOX NPs may offer a feasible and effective strategy for osteosarcoma-targeted therapy.