Abstract
Materials that respond to endogenous stimuli are being leveraged to enhance spatiotemporal control in a range of biomedical applications from drug delivery to diagnostic tools. The design of materials that undergo morphological or chemical changes in response to specific biological cues or pathologies will be an important area of research for improving efficacies of existing therapies and imaging agents, while also being promising for developing personalized theranostic systems. Internal stimuli-responsive systems can be engineered across length scales from nanometers to macroscopic and can respond to endogenous signals such as enzymes, pH, glucose, ATP, hypoxia, redox signals, and nucleic acids by incorporating synthetic bio-inspired moieties or natural building blocks. This Review will summarize response mechanisms and fabrication strategies used in internal stimuli-responsive materials with a focus on drug delivery and imaging for a broad range of pathologies, including cancer, diabetes, vascular disorders, inflammation, and microbial infections. We will also discuss observed challenges, future research directions, and clinical translation aspects of these responsive materials.