Doxorubicin and iron-doped mesoporous silica nanoparticles for chemodynamic therapy and chemotherapy of breast cancer†

Breast cancer is one of the most prevalent malignancies, necessitating the exploration of more effective synergistic treatment strategies to overcome the limitations of conventional therapies. Chemodynamic therapy (CDT) is an innovative antitumor approach that can be combined with chemotherapy to achieve potent synergistic effects. Mesoporous silica nanomaterials (MSNs) are ideal drug delivery vehicles in cancer therapy due to their unique advantages. This study presents an effective and straightforward strategy to design an intelligent drug delivery system (DDS) activated by the tumor-specific weakly acidic microenvironment to achieve efficient cancer treatment. By incorporating the chemotherapeutic drug doxorubicin (DOX) and divalent iron (Fe²⁺) into the unique mesoporous channels of MSNs, we fabricated MSNs@Fe²⁺@DOX. Under weakly acidic pH conditions, the functional components Fe²⁺ and DOX of MSNs@Fe²⁺@DOX are gradually released at the tumor site. The released Fe²⁺ can then consume hydrogen peroxide (H₂O₂) in tumor cells, increasing the levels of reactive oxygen species (ROS) and lipid peroxides through the Fenton reaction, thereby inducing ferroptosis. The combination of DOX-induced apoptosis and ferroptosis results in further enhanced cancer treatment. In vitro and in vivo experiments demonstrated that MSNs@Fe²⁺@DOX had an excellent therapeutic effect on breast cancer cells and tumor-bearing nude mice. We anticipate that this study will provide a promising biotechnological platform for combined breast cancer treatment by inducing CDT and chemotherapy.