Platinum (II) Nanofibers as Assembly-driven Inhibitors of Metabolic Adaptation in Cancer Cells

Nanostructure-based functions are omnipresent in biology and essential for the diversity of life. Despite their importance, it is difficult to establish mechanisms that define their bioactivity and rationalize them through synthetic designs. As such, strategies that connect bioactive functions through structure formation are scarce. Herein, we design a near-infrared emitting platinum (II)-tripeptide that undergoes a rearrangement using endogenous H2O2 to rapidly assemble into fibrillar superstructures. The resultant assembly inhibits the metabolism of aggressive metastatic MDA-MB-231 cells and A549 cells at the systemic level by blocking aerobic glycolysis and oxidative phosphorylation, thereby shutting down ATP production. Hence, ATP-dependent actin formation and glucose metabolite-dependent histone deacetylase activity are downregulated, leading to apoptosis. By demonstrating that assembly-driven functions can inhibit broad biological pathways, supramolecular nanostructures could offer the next generation biomedical solutions beyond conventional applications.