Recent Advances of In Situ Anticancer Nanomedicine from Enzyme‐Instructed Self‐Assembly

While conventional anticancer nanomedicine primarily focuses on using polymeric or lipid nanoparticles to deliver therapeutic agents, an emerging alternative approach is to turn the enzymes overexpressed by tumor cells as the catalysts for in situ self‐assembly within cancer cells or the tumor microenvironment. In recent years, advancements in this field have shifted the role of self‐assembling motifs from carriers of known drug molecules to a new class of anticancer therapeutics themselves. The rapid progress of this emerging field necessitates a brief review to highlight its unique concepts and features, which revert a main drug resistance mechanism to a tumor targeting advantage. Herein, recent representative examples of in situ nanomedicine generated by enzyme‐instructed self‐assembly are discussed, categorizing them based on the specific enzymes that trigger the self‐assembly process. The critical role of molecular design in optimizing therapeutic efficacy and selectivity is emphasized. In the perspective and outlook, insights into the advantages of this approach are offered, while also addressing the key challenges that must be overcome to translate these strategies toward clinical applications. This review underscores the potential of enzymatic in situ nanomedicine as a complementary strategy to molecular therapy in cancer treatment.