Multifunctional bone cement for synergistic magnetic hyperthermia ablation and chemotherapy of osteosarcoma

Abstract

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe₃O₄ nanoparticles and the antitumor drug doxorubicin (DOX/Fe₃O₄@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe₃O₄@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe₃O₄ nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe₃O₄@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe₃O₄@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe₃O₄@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.

Keywords: Chemotherapy; Magnetic hyperthermia ablation; Osteosarcoma; PMMA bone cement.