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

【Abstract】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.

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