Hydrogen Polysulfide Biosignal‐Responsive Polymersomes as a Nanoplatform for Distinguishing Intracellular Reactive Sulfur Species (RSS)

Abstract Reactive sulfur species (RSS) are a family of crucial biosignals for regulating cell processes. Among these, hydrogen polysulfide (H₂S_n, n ≥ 2) is a hallmark of tumor suppressor activation and regarded as the actual regulator to mediate sulfur‐related biology. However, high effective recognition of intracellular H₂S_n is insurmountable due to its extremely low concentration and the disturbance of RSS analogues. Here an H₂S_n‐responsive macromolecule that can distinguish H₂S_n from intracellular RSS through polymer degradation in ultrasensitive and highly selective manner is reported. This kind of polymers can further self‐assemble into vesicular nanostructure. Upon cell uptake, they can be function as “all‐in‐one” H₂S_n‐nanoplatforms, in order to fulfill multiple ambitious tasks including monitoring the H₂S_n biosynthetic pathways, unraveling the puzzles of H₂S_n‐mediated cellular events, and conducting H₂S_n pathological milieu‐specific drug delivery.