Targeting nanoplatform synergistic glutathione depletion-enhanced chemodynamic, microwave dynamic, and selective-microwave thermal to treat lung cancer bone metastasis.

Abstract

Once bone metastasis occurs in lung cancer, the efficiency of treatment can be greatly reduced. Current mainstream treatments are focused on inhibiting cancer cell growth and preventing bone destruction. Microwave ablation (MWA) has been used to treat bone tumors. However, MWA may damage the surrounding normal tissues. Therefore, it could be beneficial to develop a nanocarrier combined with microwave to treat bone metastasis. Herein, a microwave-responsive nanoplatform (MgFe₂O₄@ZOL) was constructed. MgFe₂O₄@ZOL NPs release the cargos of Fe³⁺, Mg²⁺ and zoledronic acid (ZOL) in the acidic tumor microenvironment (TME). Fe³⁺ can deplete intracellular glutathione (GSH) and catalyze H₂O₂ to generate •OH, resulting in chemodynamic therapy (CDT). In addition, the microwave can significantly enhance the production of reactive oxygen species (ROS), thereby enabling the effective implementation of microwave dynamic therapy (MDT). Moreover, Mg²⁺ and ZOL promote osteoblast differentiation. In addition, MgFe₂O₄@ZOL NPs could target and selectively heat tumor tissue and enhance the effect of microwave thermal therapy (MTT). Both in vitro and in vivo experiments revealed that synergistic targeting, GSH depletion-enhanced CDT, MDT, and selective MTT exhibited significant antitumor efficacy and bone repair. This multimodal combination therapy provides a promising strategy for the treatment of bone metastasis in lung cancer patients.