Selenium operates as a redox-active element that cycles among Se(− 2), Se(0), Se(+ 2), and Se(+ 4) states, and this intrinsic variability provides a direct route for programming electron transfer in therapeutic materials. Recent advances have expanded selenium therapeutics across molecular, nanoscale, and macromolecular formats, increasing the need for a unified chemical basis for comparison and design of selenium-based drugs. Across small molecules, nanoparticles, and polymer networks, the same chemistry-centered descriptors (species, bonding motif, placement, and trigger window) determine how selenium interprets oxidative input and how this input is converted into catalytic, interfacial, or structural responses. Organoselenium motifs regulate peroxide handling and enzyme-linked signaling through reversible Se(− 2) to Se(+ 4) transitions. Elemental Se(0) nanoparticles generate interfacial redox behavior, which is defined by ligand coordination and corona chemistry. Polymeric systems embed selenium within dynamic linkages that couple oxidative input to bond exchanges and time-dependent degradation. Existing reviews have often treated these platforms in isolation, which limits cross-scale comparisons and delays the translation of chemistry-guided design principles. In this review, these relationships are organized into a design-rule framework in which selenium species, defined by chemical form together with oxidation state, bonding motif, placement, and trigger window, establish a coherent chemical logic across scales. To improve cross-study comparability, we highlight practical reporting parameters that specify the dominant selenium speciation and bonding motif, microenvironmental trigger conditions, and architecture-dependent descriptors, including nanoparticle surface and corona features, polymer linkage density, and reversibility. This perspective provides a unified basis for evaluating and comparatively guiding selenium-based therapeutic platforms using quantifiable chemical parameters. Reversible Se(− 2), Se(0), and Se(+ 4) states enable programmable redox control in selenium-containing materials. Selenium species, bonding motifs, placement, and trigger windows collectively determine therapeutic behavior. Se(0) interfaces and diselenide networks convert oxidative cues into controlled therapeutic responses.
Koo et al. (Wed,) studied this question.