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

Abstract

Abstract Reactive sulfur species (RSS) are a family of crucial biosignals for regulating cell processes. Among these, hydrogen polysulfide (H 2 S 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 H 2 S n is insurmountable due to its extremely low concentration and the disturbance of RSS analogues. Here an H 2 S n ‐responsive macromolecule that can distinguish H 2 S 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” H 2 S n ‐nanoplatforms, in order to fulfill multiple ambitious tasks including monitoring the H 2 S n biosynthetic pathways, unraveling the puzzles of H 2 S n ‐mediated cellular events, and conducting H 2 S n pathological milieu‐specific drug delivery.