A novel nanofibrous mat featuring an ultraviolet (UV)-induced CO2-responsive behavior was fabricated via electrospinning and used as a controlled drug release system. First, a random copolymer for electrospinning, poly(N,N-diethylaminoethyl acrylamide-co-N-benzylacrylamide-co-N,N-dimethyl-N-(2-nitrobenzyl)-ethaneamine acrylamide-co-4-acryloyloxy benzophenone) [P(DEEA-co-BA-co-DMNOBA-co-ABP)], was prepared based on pentafluorophenyl esters via an "active ester-amine" chemistry reaction. Subsequently, doxorubicin hydrochloride (DOX)-loaded P(DEEA-co-BA-co-DMNOBA-co-ABP) nanofibers were fabricated, yielding a new drug-loaded nanofibrous mat as a potential wound dressing. These DOX-loaded nanofibers can respond to UV irradiation and CO2 stimulation. Interestingly, without UV irradiation, the fabricated nanofibers cannot exhibit any responsiveness. Therefore, the majority of the DOX was steadily stored in the nanofibers, even in the presence of CO2. However, upon UV irradiation, the CO2-responsive behavior of the nanofibers was activated and the prepared nanofibers swelled slightly, resulting in the release of around 42% DOX from the nanofibers. Upon further purging with CO2, the release amount of DOX from the nanofibers could reach up to approximately 85%, followed by the morphological transition from a nanofibrous mat to a porous hydrogel film. (c) 2019 Wiley Periodicals, Inc.