Responsive biomaterials for tumor sensing and therapy

An increasing number of smart biomaterials have garnered significant attention in biomedical applications owing to their self-repair capabilities, adaptability to complex environments, and responsiveness to external stimuli. These properties enable these materials to exhibit on-demand intelligence in intricate biological settings. Specifically, for smart biomaterials that autonomously respond to the specific physicochemical properties of the tumor microenvironment (TME) as well as bioactive molecules or functional biomacromolecules within it, a systematic summary of their inherent structural advantages and the unique characteristics of the TME is urgently needed. This review focuses on responsive biomaterials, encompassing inorganic, organic, and organic-inorganic hybrid biomaterials. By analyzing their surface-active sites, functional groups, molecular configurations, and other relevant characteristics, this review aims to elucidate the structure-activity relationship between the structural features of responsive biomaterials, their chemical reactivity, and their adaptive responsiveness to the complex TME. Additionally, intelligent design and optimization strategies are also discussed to enhance the practicality of responsive biomaterials in complex biological environments. We anticipate that this review will assist researchers in gaining a deeper understanding of responsive biomaterials and facilitate the development of more effective and advanced multifunctional tools for tumor bioimaging, biosensing, and disease therapy. • Structure-activity relationships between structural characteristics, chemical reactivity, and self-response to the tumor microenvironment in smart biomaterials. • Design and optimization strategies for self-responsive biomaterials. • Self-responsive biomaterials designed based on the tumor microenvironment for tumor imaging and therapy.