Dual peptide-engineered and gadolinium-doped polydopamine particles as targeted nanotheranostics for the treatment of osteosarcoma and related osteolysis

Abstract

The treatment of malignant bone tumors such as osteosarcoma and tumor-associated bone destruction is challenging in clinic. Here, we designed a type of bone-targeted nanotheranostics to treat osteosarcoma. A bone targeting peptide consisting of eight aspartic acids and a tumor targeting peptide were conjugated onto polydopamine nanoparticles bearing gadolinium ions at different molar ratios. The optimized nanoformulation showed high photothermal efficiency, bone targeting affinity, and were efficiently accumulated at tumor site and osteolysis lesions after systematic administration. In addition, the peptide conjugated on nanoparticle surface efficiently inhibited osteoclast formation and bone destruction both in vitro and in vivo. As a result, the prepared nanoparticles combination with near-infrared laser irradiation efficiently inhibited tumor growth and tumor-associated bone resorption in an osteosarcoma xenograft mice model. This study provides a new nanotheranostic to treat osteosarcoma and related osteolysis.