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 Senhanced tumor chemotherapy.

Pyroptosis is a proinflammatory form of cell death mediated by gasdermin family members, and is a powerful tool against cancer. Herein，a pH-responsive doxorubicin (DOX) encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticle...

Colorectal cancer is one of the most common causes of cancer‐related deaths worldwide. Ferroptosis is a non‐apoptotic form of regulated cell death that can be triggered by excessive lipid peroxidation and provides an alternative cancer treatment option. To design ferroptosis‐targeted nanomedicine, a new type of nanoparticle is synthesized. The antineoplastic agent simvastatin (SIM) and specifically designed short hairpin RNA (shRNA) are co‐loaded into zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticles coated with poly(carboxybetaine methacrylate) (PCBMA). The constructed shRNA/ZIF‐8@PCBMA‐SIM nanoparticles effectively eliminate human colorectal carcinoma cells in vivo, showing superior cytotoxicity against tumors owing to their improved targeting ability and the high retention of antineoplastic agents delivered at tumor sites. Furthermore, SIM and shRNA downregulate the expression of ferroptosis‐related enzymes 3‐hydroxy‐3‐methylglutaryl‐CoA reductase and glutathione peroxidase 4, thus, triggering ferroptosis in cancer cells. Given that SIM is already approved for clinical use, and shRNA offers high potency to downregulate the cystine/glutamate antiporter (x‐CT) system protein (subunit SLC7A11), shRNA/ZIF‐8@PCBMA‐SIM nanoparticles show great clinical potential to treat colorectal cancer via ferroptosis. This presents an alternative therapy that addresses the limitations of chemotherapy.