Design and evaluation of a multi-responsive dual-modality bone-targeted drug delivery vehicle for the treatment of osteosarcoma.

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.