Assembly/disassembly-based targeting protein degradation systems for cancer therapy

Targeted protein degradation (TPD) is an innovative strategy for selectively eliminating pathogenic proteins, enabling precise degradation of once-undruggable targets in cancer therapy. However, current TPD molecules are often limited by poor tumor targeting and the need for high doses. To overcome these limitations, assembly/disassembly-based TPD systems have been proposed to effectively degrade proteins of interest and enhance therapeutic efficacy. Herein, we summarize the recent advances in such TPD systems and categorize the strategies employed, including nanosphere morphology of assembled TPD systems, nanofiber morphology of assembled TPD systems, carrier-mediated TPD release systems, and stimulus-induced free TPD molecule formation nanosystems. Finally, we outline future directions and identify the remaining challenges in assembly/disassembly-based TPD systems. • Assembly/disassembly-based TPD systems enhance targeted cancer therapy. • Nanosphere and nanofiber TPD systems improve retention and tumor targeting. • Carrier-mediated systems enable controlled TPD molecule release. • Stimulus-responsive systems trigger precise protein degradation in tumors. • Strategies overcome limitations of conventional TPD therapeutics.