Metal-Coordination Directs the Self-Assembly of Terpyridine-Peptide Conjugates into Multifunctional Nanoplatforms with Potent In Vitro Antitumor Effects

The complexity of cancer treatment calls for multimodal nanoplatforms integrating multiple therapeutic functions. Herein, we design a metal-ion-directed self-assembly strategy using a terpyridine-functionalized peptide (TyD) and demonstrate that coordination with different metal ions (Cu 2+, Mn 2+, Fe 2+ ) simultaneously regulates nanostructure formation and dictates their enzyme-mimetic, DNA-binding, and photothermal properties. Notably, the TyD-Cu 2+ complex emerged as a uniquely multifunctional platform, enabling efficient reactive oxygen species (ROS) generation, glutathione (GSH) depletion, DNA binding and cleavage, and exhibiting a high photothermal conversion efficiency (η = 33%). Relying on these integrated, metal-ion-dependent functionalities, we constructed a nanoplatform that synergistically combines chemodynamic therapy, photothermal therapy, and DNA-damaging interventions. This work establishes a metal-ion-tunable strategy for creating multifunctional peptide-based nanomaterials with potent antitumor effects in vitro, offering a promising material platform for further development in cancer therapy.