A nanotherapy designed to release rapamycin specifically in response to an inflammatory microenvironment effectively reduces abdominal aortic aneurysm (AAA) expansion in rats. Rapamycin was encapsulated in a biomimetic cloaking of macrophage cell membrane to create a nanoparticle that would release drug molecules in response to high levels of reactive oxygen species (ROS). Peptide ligands were incorporated to target the intravenously injected nanoparticles to aneurysms. The nanotherapy inhibited calcification, oxidative stress and apoptosis in cells associated with the development of AAAs and prevented aneurysm expansion more effectively than a control nanotherapy that was not responsive to ROS. The nanotherapy had a good safety profile in preliminary safety tests and has the potential to be developed into a targeted therapy for other vascular diseases.