A biodegradable calcium sulfite nanoreactor for pH triggered gas therapy in combination with chemotherapy

As a gasotransmitter, endogenous sulfur dioxide (SO₂) plays an important role in cardiovascular regulation. In addition, excessive SO₂ can react with overexpressed hydrogen peroxide (H₂O₂) in tumor cells to generate toxic radicals, which can induce severe oxidative damage to tumor cells and result in cell apoptosis. This highlights the potential of SO₂ in oncotherapy. However, the limited availability of endogenous H₂O₂ and uncontrolled release of SO₂ gas significantly impede the effectiveness of SO₂ gas therapy. To address this challenge, a biodegradable calcium sulfite (CS) nanocarrier loaded with 10-hydroxycamptothecin (HCPT) was developed for tumor pH-triggered SO₂ gas therapy in combination with chemotherapy. This nanoreactor could be degraded in an acidic tumor microenvironment to release SO₂ gas and the HCPT drug. The released SO₂ gas induced serious oxidative damage to tumor cells by depleting glutathione (GSH) and generating toxic radicals through a reaction with intracellular H₂O₂. Simultaneously, the HCPT drug promoted tumor cell apoptosis through chemotherapy and boosted SO₂ gas therapy by elevating the H₂O₂ level within the tumor cells. Consequently, the combination of SO₂ gas therapy and chemotherapy provided a promising approach for effective tumor treatment.