Recent Advances in Stimuli-Responsive Self-Immolative Polymers for Drug Delivery and Molecular Imaging

Stimuli-responsive self-immolative polymers (SIPs) represent a unique class of polymers that can undergo controlled, sequential head-to-tail depolymerization upon specific stimuli. Since their inception, they have evolved over two decades to become one of the most attractive polymer types. With their characteristic feature of “one stimulus, multiple responses”, SIPs inherently possess the ability to serve as chemical amplifiers, which can amplify weak chemical or biological signals. This feature promises higher stimulus sensitivity, greater selectivity for specific microenvironments, and the potential to generate more persistent, extensive, and significant responses while consuming fewer stimuli sources. This Review summarizes the latest research advancements in stimuli-responsive SIPs for drug delivery and molecular imaging over the past five years. Regarding the structure of SIPs, we briefly overview the updates in self-immolation units, end-cap moieties, and sequence of SIPs. In terms of applications, we focus on the possible biological applications of SIPs in drug delivery for disease treatment and potential imaging methods. Finally, we provide a brief perspective of potential future directions for SIPs in these applications.