In situ supramolecular self-assembly of a perylene diimide derivative in mitochondria for cancer cell ferroptosis

Abstract

Self-assembly in subcellular organs to regulate their metabolic processes for regulated cell death has become an increasingly significant topic but remains a formidable challenge in chemical and biological science. Herein, an in situ self-assembly system in mitochondria of cancer cells was successfully constructed using a perylene diimide derivative (PDI-NH₂) that could self-assemble into nanoparticles with multi-negatively charged molecules in mitochondria of cancer cells, resulting in metabolic dysfunction for cancer cell ferroptosis. Owing to the direct interaction between mitochondria and in situ formed nanoparticles, mitochondrial function would be damaged, impairing cellular metabolism systems and iron homeostasis, which can ultimately lead to elevated ROS levels, lipid peroxidation and the downregulation of the GPX4 protein for cancer cell ferroptosis. Finally, this self-assembly process could also be realized in vivo to suppress the growth of tumors. This work reveals that in situ self-assembly in subcellular organelles could interfere with the metabolic process for regulating cellular behavior, providing strong support for supramolecular self-assembly in bio-application.