Mesoporous Organosilica-Based Hydrogen Sulfide Nanogenerator for Enhanced Tumor Chemotherapy

Conventional chemotherapy is bothered by systematic toxicity and confined therapeutic effects. Gas therapy has emerged as a potent tumor treatment, and hydrogen sulfide (H 2 S), a traditional gasotransmitter, has been found to show a tumor inhibition effect. Therefore, we established a mesoporous organosilica-based H 2 S 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 H 2 S, further resulting in the degradation of nanogenerator and DOX release. GSH consumption and H 2 S 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 H 2 S-enhanced tumor chemotherapy.