TyD-Cu2+ peptide nanoplatforms self-assemble, delivering potent in vitro antitumor effects via multimodal mechanisms.

The complex nature of cancer necessitates multimodal therapeutic strategies that integrate diverse functions into a single platform. Traditional treatments often face limitations such as off-target toxicity, drug resistance, and insufficient efficacy. Peptide self-assembly offers a promising route for developing advanced nanomaterials, leveraging their biocompatibility and tunable properties. However, designing systems that can simultaneously regulate nanostructure formation and dictate multiple therapeutic functionalities, especially through simple metal-ion coordination, remains a significant challenge. This study explores a novel approach using terpyridine-functionalized peptides to address this gap, aiming to create versatile nanoplatforms for enhanced antitumor efficacy.

Researchers designed a terpyridine-functionalized peptide, designated TyD, to investigate metal-ion-directed self-assembly. They coordinated TyD with different metal ions: Cu2+, Mn2+, and Fe2+. The resulting metal-peptide complexes were then characterized for their ability to form nanostructures and assessed for various therapeutic properties. Key functionalities evaluated included enzyme-mimetic activity, DNA-binding and cleavage capabilities, and photothermal conversion efficiency. The TyD-Cu2+ complex, specifically, was subjected to in vitro testing to determine its efficacy in reactive oxygen species (ROS) generation, glutathione (GSH) depletion, and overall antitumor effects.

Coordination with different metal ions was found to simultaneously regulate nanostructure formation and dictate the therapeutic properties of the TyD conjugates. The TyD-Cu2+ complex emerged as a uniquely multifunctional platform, demonstrating efficient ROS generation and significant GSH depletion. It also exhibited robust DNA binding and cleavage capabilities, crucial for inducing cellular damage. Furthermore, the TyD-Cu2+ complex showed a high photothermal conversion efficiency (η = 33%), indicating its potential for heat-mediated therapy. These integrated, metal-ion-dependent functionalities allowed for the construction of a nanoplatform that synergistically combines multiple therapeutic modalities. > The TyD-Cu2+ complex uniquely integrated chemodynamic therapy, photothermal therapy, and DNA-damaging interventions, showcasing potent in vitro antitumor effects.