Copper-Driven Allosteric and Self-Encapsulating Polymers for Tumor-Specific Fluorescence Imaging and Dual-Enzymatic Cancer Therapy.

Abstract

Metal ion-mediated redox process and protein folding are fundamental to numerous physiological functions. However, the mechanisms underlying copper ion interactions with macromolecules remain insufficiently understood, and the therapeutic potential of polymer-copper complexes is largely underexplored. Here, a biomimetic metallopolymer is reported in which copper ion coordination induces a conformational transition from β-sheet to α-helix, accompanied by oxidative self-encapsulation and fluorescence quenching. By leveraging the tunable intrinsic fluorescence of the polymer, the first systematic elucidation of the coordination interaction mechanism between polythiols and copper ions is presented. This interaction enhances the structural stability, catalytic efficiency, membrane activity, and drug loading capacity. Furthermore, the polymer-copper complex demonstrates tumor-activated fluorescence and dual enzyme-mimetic activities, enabling precise tumor imaging and multimodal therapeutic efficacy both in vitro and in vivo. This work provides new insights into the interactions between macromolecules and metal ions and establishes a versatile and intelligent nanosystem for advanced disease diagnostics and therapeutics.