Glutathione-responsive mesoporous silica nanocarriers for chemo–photothermal–photodynamic therapy of cancer

A series of antitumor therapies such as chemotherapy, photothermal therapy, and photodynamic therapy have certain limitations when applied alone. Herein, the chemotherapy drug doxorubicin (DOX) and photosensitizer new indocyanine green (IR820) were loaded into mesoporous silica nanoparticles (MSNs), and it was wrapped by manganese dioxide (MnO 2 ) on the surface. Optimization of the synthesis conditions by Box–Behnken design (BBD) generated DOX-IR820@MSN–MnO 2 nanoparticles with a high loading capacity. The experiments suggested that the nanocomposites had tumor microenvironment response characteristics and excellent photodynamic and photothermal properties. It can significantly regulate the level of glutathione and reduce the antioxidant effect of cells to enhance the photodynamic effect. NIR laser irradiation increases the temperature and accelerates drug release. The relative cell viability in the multi-modal combination therapy group almost disappeared at 17.20%. Combined tumor microenvironment response and multi-modal therapy show unique advantages in inhibiting tumor cell proliferation and have promising applications and development potential in cancer treatment. Graphical Abstract