Abstract: | Abnormal physiological conditions provide an ideal stimulus for the design of responsive hydrogels which function as controlled and site‐specific release of drugs. Here, an injectable reactive oxygen species (ROS) responsive self‐healing hydrogel based on tetra‐poly(ethylene glycol)‐b‐oligo (l ‐methionine) (t‐PEG56‐b‐OMethn) synthesized by a novel and facile method is reported. The hydrophobic interactions between the side chains of l ‐methionine make the polymer chains crosslinked and lead to the formation of hydrogels which can be injected and self‐healed, meanwhile, the cross‐linker also provides a hydrophobic domain to encapsulate Dox. In presence of ROS, the side chain of l ‐methionine can be oxidized to methionine sulfoxide. The side chain of l ‐methionine is changed accordingly from hydrophobic to hydrophilic. As a result, both the hydrophobic domain and the hydrogel itself are destroyed. The controlled release of Dox by ROS at site‐specific is realized. The excellent biocompatibility of hydrogel based on t‐PEG56‐b‐OMethn indicates the door of the potential application in controlled release of drug in a truly physiological environment. |