Hydrogen sulfide (H2S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H2S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol-triggered macromolecular H2S donors. By combining this approach with polymerization-induced self-assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm-like morphology. The thiol-reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl-protected perthiol groups using a three-step procedure throughout which both morphologies remained intact. The H2S releasing properties were subsequently studied, with both spherical and worm-like nanoparticulate donors shown to successfully release H2S in the presence of the model thiol, l-cysteine. In addition, the donor polymers were shown to effectively increase H2S inside cells, upon exposure to biologically relevant endogenous thiol levels. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1982-1993