Tumor microenvironment-responsive polymer with chlorin e6 to interface hollow mesoporous silica nanoparticles-loaded oxygen supply factor for boosted photodynamic therapy

Abstract

Cancer treatment has always been a big problem for people. With the application of photodynamic therapy, the problem has been alleviated. However, the problem of tumor hypoxia affecting photodynamic therapy has been waiting to be resolved. Therefore, we report here that a redox nanocarrier (called RN) is prepared by hollow mesoporous silica sphere (HMSNs) and a redox-responsive polymer ligand. The nanocarrier is loaded with metformin and catalase, and the polymer is linked to the photosensitizer chlorin e6 (Ce6). Metformin inhibits the mitochondrial respiration of cancer cells, reducing the activity of cancer cells and increasing the oxygen concentration required for photodynamic therapy. Not only the effect of photodynamic therapy is enhanced, but also the effect of chemotherapy is increased to achieve super additive treatment. These RNs exhibit not only low cytotoxicity but also high biocompatibility in vitro experiments. In vitro Ce6 release studies have shown a higher release in the presence of glutathione (GSH). Confocal microscopy can further indicate that the nanoparticles are carried to the area around the nucleus of the cancer cells. In addition, treatment with a mouse tumor model demonstrated that RN has an effective therapeutic effect on tumors.