The application belongs to the technical field of biological
medicine. More specifically, it relates to a preparation and application of in-situ imaging
DNA-PROTAC based on strand displacement activation. The novel
DNA-PROTAC provided by the application is designed by three modules, which are respectively recruitment module A (E3 ligase ligand-
linker-clicking group), locking module B (
aptamer-shielded chain double-stranded complex) and activation module C (
DNA single strand), three physically separated components, so that the degradation activity is completely silent in the delivery stage. Only after the
drug reaches the target area, the in-situ
assembly of recruitment module A and locking module B can be triggered by adding activation module C to trigger the strand displacement reaction, thereby effectively avoiding the non-
specific activity of traditional degrading agents in the
whole body circulation, and significantly reducing the off-target
toxicity. In addition, the application converts the large conjugate into multiple independent components with medium and small molecular weights by physical splitting, overcoming the macromolecular delivery barrier.