Background <p>Chemotherapy is a major method to treat breast cancer. However, the multidrug resistance of cancer, the low tumor accumulation of anticancer drugs, and the serious side effects result in the unsatisfactory therapeutic outcomes of chemotherapy. Collaborative therapy containing chemotherapy, hunger therapy, chemodynamic therapy and photothermal therapy could be a promising way to efficiently conduct tumor combination therapy.Chemotherapy is a major method to treat breast cancer. However, the multidrug resistance of cancer, the low tumor accumulation of anticancer drugs, and the serious side effects result in the unsatisfactory therapeutic outcomes of chemotherapy. Collaborative therapy containing chemotherapy, hunger therapy, chemodynamic therapy and photothermal therapy could be a promising way to efficiently conduct tumor combination therapy.</p> Objectives <p>In this study, a novel pH/redox responsive ultralarge mesoporous silica-based drug delivery system (denoted as PUGFP) was constructed to synergistically treat breast cancer.</p> Methods <p>Chemotherapeutic agent paclitaxel (PTX) were loaded into the pores of ultra-large mesoporous silica. Glucose oxidase (GOD), tannic acid (TA)/Fe (III) ligand and polydopamine (PDA) were loaded onto the silica as catalyst of glucose oxidation, generator of Fenton reaction and photosensitizer, respectively. PDA absorbs near-infrared light (NIR) and converts it into thermal energy, causing local temperature rise and achieving ablation of tumor cells.</p> Results <p>The production of Fe (II) induced by glutathione improved the efficiency of the Fenton reaction resulting in significant tumor inhibition. The GOD-induced starvation therapy not only cuts off energy supply but also produces a large amount of hydrogen peroxide to kill tumor cells. The results of cell experiments demonstrated that the cell viability was 11.98% in PUGFP (50 μg/mL) with NIR irradiation group.</p> Conclusion <p>PUGFP had excellent biocompatibility, high safety, and strong killing ability against tumor cells, presenting a promising system for combination therapy. Chemotherapy is a major method to treat breast cancer. However, the multidrug resistance of cancer, them low tumor accumulation of anticancer drugs, and the serious side effects result in the unsatisfactory therapeutic outcomes of chemotherapy. Collaborative therapy containing chemotherapy, hunger therapy, chemodynamic therapy and photothermal therapy could be a promising way to efficiently conduct tumor combination therapy. In this study, a novel pHed drug delivery system (denoted as PUGFP) was constructed. Chemotherapeutic agent paclitaxel (PTX) were loaded into the pores of ultra-large mesoporous silica. Glucose oxidase (GOD), tannic acid (TA)/Fe (III) ligand and polydopamine (PDA) were loaded onto the silica as catalyst of glucose oxidation, generator of Fenton reaction and photosensitizer, respectively. PDA absorbs near infrared light (NIR) and converts it into thermal energy, causing local temperature rise and achieving ablation of tumor cells. Furthermore, the production of Fe (II) induced by glutathione improved the efficiency of the Fenton reaction resulting in significant tumor inhibition. The GOD-induced starvation therapy not only cuts off energy supply but also produces a large amount of hydrogen peroxide to kill tumor cells. The results of cell viability and animal experiments demonstrated that PUGFP had excellent biocompatibility, high safety, and strong killing ability against tumor cells. In summary, the multifunctional drug delivery system presented a promising system for combination therapy.</p>