Feature-Enhanced artificial neutrophils for Dual-Modal MR/NIR Imaging-Guided cancer therapy

Neutrophils release neutrophil elastase (ELANE) to kill a wide range of cancer cells through proteolytically liberating the CD95 death domain (DD) and initiating apoptotic pathway in cancer cells. However, current neutrophil-inspired strategies are restricted to single reactive oxygen species (ROS)-based killing and rarely involve coordinated multi-path tumor killing. Herein, we develop feature-enhanced artificial neutrophils (aNeu) to improve tumor therapy via dual-modal MR/NIR imaging-guided combined actions of cytotoxic porcine pancreatic elastase (PPE), ROS and the triggered protective immunity. We construct aNeu by loading PPE and NIR-responsive IR780 into glutathione-unlocked hollow MnO2 nanoparticles and then coating with neutrophil membrane. After stimulation-responsive activation inside tumor cells, the as-prepared aNeu can exhibit robust tumor killing effect and elicit adaptive immune response to promote tumor elimination. Moreover, MR/NIR imaging enable aNeu to monitor payload release and to anticipate therapeutic outcome. This feature-enhanced aNeu offers a new paradigm for neutrophil-inspired tumor therapy.