Abstract

The peroxide bridge present in dihydroartemisinin (DHA) can be efficiently catalyzed by transition metals, resulting in the generation of reactive oxygen species (ROS) that exhibit potent anti-tumor effects. In this study, we developed a novel nanocarrier system by loading DHA into hollow mesoporous silica nanoparticles (HMSN) and incorporating a tumor microenvironment-sensitive gating system consisting of TA/Fe complex. This newly developed nanocarrier, termed HMSN-DHA@TA/Fe, demonstrated remarkable anti-tumor effects specifically within the tumor microenvironment. The release profile of HMSN-DHA@TA/Fe was evaluated, revealing a pH-responsive release mechanism, with a release rate of 42.5% observed at pH= 5. Importantly, cellular experiments demonstrated that the survival ratio of HMSN-DHA@TA/Fe on normal cells exceeded 85%. Conversely, the survival ratio of tumor cells was significantly reduced to only 50%, highlighting the selective cytotoxicity of the nanocarrier towards cancer cells. Furthermore, the inhibitory efficacy of HMSN-DHA@TA/Fe against solid tumors was evaluated in vivo, demonstrating its potent anti-tumor activity. The nanocarrier exhibited a significant ability to suppress tumor growth, underscoring its potential as a promising therapeutic strategy for solid tumors.

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