Noninvasive detection of biological responses to reactive oxygen species (ROS) in vivo could shed light on mechanisms at work in diverse areas like developmental dynamics, therapeutic effectiveness, drug discovery, pathogenic processes, and disease prevention. Research on ROS is usually dependent on in vitro models without translational relevance. Nanoscale (<100 nm) particulates are attractive carriers and platforms for biosensor technology due to their small size, flexible assembly, and favorable toxicity profiles. Intracellular signalling pathways activated in response to ROS have been well documented and mechanisms elaborated. Likewise, there is a wealth of genetic reporter systems that utilize fluorescent proteins capable of being monitored noninvasively. We combined these elements into a platform technology that utilizes nanoparticle-tethered synthetic genetic elements that respond to cellular response elements to report endogenous responses to oxidative insult through fluorescent gene expression. We envision the future of this technology to play a research role quantifying oxidative stress in vivo and a future clinical role as an automated theragnostic for ROS-related diseases. The production of this nanobiosensor technology utilizes off-the-shelf components and can be carried out in a molecular biology laboratory. Assessment of fluorescent protein expression can be done with noninvasive imaging and quantitative protein expression analysis. This is a flexible nanoparticle-based reporter system for monitoring in vivo responses to ROS.