Glycosidase-activated H₂S donorsto enhance chemotherapy efficacy

Hydrogen sulfide (H₂S) plays a critical role in cancer biology. Herein, we developed a series of glycosidase-triggered hydrogen sulfide (H₂S) donors by connecting sugar moieties (including glucose, galactose and mannose) to COS donors via a self-immolative spacer. In the presence of corresponding glycosidases, H₂S was gradually released from these donors in PBS buffer with releasing efficiencies from 36 to 67 %. H₂S release was also detected by H₂S probe WSP-1 after treatment HepG2 cells with Man1. Cytotoxicities of these glycosylated H₂S donors were evaluated against HepG2 by MTT assay. Among them, Man1 and Man2 exhibited an obvious reduction of cell viability in HepG2 cells, with cell viability as 37.6 % for 80 μM of Man. Consistently, significant apoptosis was observed in HepG2 cells after treatment with Man1 and Man2. Finally, We evaluated the potential of Man1 for combination therapy with doxorubicin. A synergistic effect was observed between Man1 and Doxorubicin in HepG2 and Hela cells. All these results indicated glycosidase-activated H₂S donorshave promising potential for cancer therapy.