Magnetothermal‐responsive drug release bone cement based on EGFR ‐mutated lung cancer bone metastases

Abstract Introduction The incidence and mortality of lung cancer (LC) are the highest among malignant tumors, and patients with advanced LC are often accompanied by bone metastasis (BoM). For epidermal growth factor receptor ( EGFR )‐mutated LC‐BoM, patients benefit more when the EGFR ‐tyrosine kinase inhibitor (TKI, e.g., Osimertinib) is combined with the bone regulator (e.g., zoledronic acid). However, the systemic side effects of Osimertinib and zoledronic acid should not be neglected. Methods First, we developed the polymethyl methacrylate/calcium phosphate cement/Osimertinib bone cement (PMMA/CPC/Osi) in order to better mechanical and biological properties. Second, the zoledronic acid‐loaded magnetic responsive mesoporous silica nanomaterials (MSNs) (Fe 3 O 4 @SiO 2 @Zol) were prepared to prolong the drug release and achieve controlled release. Third, a final bone cement system was constructed by mixing PMMA/CPC/Osi bone cement and Fe 3 O 4 @SiO 2 @Zol. Results We improved the Osimertinib releasing and anti‐tumor performance by developing PMMA/CPC/Osimertinib bone cement. Combined with Fe 3 O 4 @SiO 2 @Zol, the bone cement was given biphasic release function to improve bone metabolism and repair. Finally, a novel bone cement system with magnetic controlled dual‐drug release function was built. Conclusion Our magnetothermal‐responsive dual‐drug release bone cement, characterized by excellent mechanical features, anti‐tumor performance and biological activity, possesses broad application outlooks.