Mesoporous Organosilica-Based Hydrogen Sulfide Nanogenerator for Enhanced Tumor Chemotherapy

Abstract

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.

Evaluation of the Ocular Safety of Hollow Mesoporous Organosilica Nanoparticles with Different Tetrasulfur Bond Content

“…Tetrasulfur bonds can react with GSH to result in the degradation of HMSNs and the consumption of intracellular GSH and simultaneously release H 2 S, which can induce cell apoptosis at high concentration. 60 , 61 In this study, it was proved that HMSN-E could react with GSH to generate H 2 S in vitro. Herein, a WSP-1 (H 2 S probe) was used to detect intracellular generation of H 2 S in HREC.…”

“…H 2 S is a gasotransmitter that regulates several pathophysiological processes. 60 , 61 High H 2 S concentrations can induce tumor cell death via various mechanisms, 62 , 63 suggesting that high H 2 S concentrations might exert potential toxicity on normal tissue cells. Therefore, in this study, HMSNs with different tetrasulfur bond contents were prepared and characterized.…”