Stimulus-responsive drug delivery systems generally aim to release the active pharmaceutical ingredient (API) in response to specific conditions and have recently been explored for disease treatments. These approaches can also be extended to molecular imaging to report on disease diagnosis and management. The stimuli used for activation are based on differences between the environment of the diseased or targeted sites, and normal tissues. Endogenous stimuli include pH, redox reactions, enzymatic activity, temperature and others. Exogenous site-specific stimuli include the use of magnetic fields, light, ultrasound and others. These endogenous or exogenous stimuli lead to structural changes or cleavage of the cargo carrier, leading to release of the API. A wide variety of stimulus-responsive systems have been developed—responsive to both a single stimulus or multiple stimuli—and represent a theranostic tool for disease treatment. In this review, stimuli commonly used in the development of theranostic nanoplatforms are enumerated. An emphasis on chemical structure and property relationships is provided, aiming to focus on insights for the design of stimulus-responsive delivery systems. Several examples of theranostic applications of these stimulus-responsive nanomedicines are discussed.
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