Abstract
Conventional chemotherapy is bothered by systematic toxicity and confined therapeutic effects. Gas therapy has emerged as a potent tumor treatment, and hydrogen sulfide (H2S), a traditional gasotransmitter, has been found to show a tumor inhibition effect. Therefore, we established a mesoporous organosilica-based H2S nanogenerator (MON-TPGS-DOX). Tetrasulfide bond-incorporated mesoporous organosilica nanoparticles were modified with d-α-tocopheryl polyethylene glycol succinate (TPGS), namely, MON-TPGS, and then loaded with doxorubicin (DOX) to obtain the nanogenerator. Tetrasulfide bonds in the nanogenerator could be triggered by glutathione (GSH) to release H2S, further resulting in the degradation of nanogenerator and DOX release. GSH consumption and H2S release led to oxidative stress in 4T1 cells, activation of apoptotic signaling cascades, and enhanced cell-killing effect. Furthermore, the nanogenerator effectively suppressed tumor growth in a tumor-bearing mice model with good biosafety, providing a promising approach for H2S-enhanced tumor chemotherapy.
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