Self-assembly for cuproptosis-based cancer therapy and imaging.

Abstract

Cuproptosis, a copper-dependent programmed cell death pathway, has emerged as a promising strategy for cancer therapy. While previous reviews have primarily focused on the fundamental mechanisms of cuproptosis and the development of inducing agents, the self-assembly-driven, stimuli-responsive cuproptosis nanoplatforms have remained relatively underexplored. To fill this gap, this review provides a comprehensive analysis of recent advancements in stimuli-responsive, dynamic self-assembly nanosystems for cuproptosis-based cancer therapy and imaging. We begin by elucidating the molecular mechanisms that underpin cuproptosis, followed by a systematic exploration of the design principles behind self-assembly-based cuproptosis inducers. These inducers leverage selective copper-ion coordination chemistry, coupled with diverse intermolecular forces, to enable precise spatiotemporal regulation. Furthermore, we highlight how these nanoassemblies undergo intelligent structural and functional transformations in response to both endogenous and exogenous stimuli, enabling controlled activation of cuproptosis. This review also explores breakthrough applications that integrate cuproptosis with synergistic therapeutic strategies and imaging guidance, highlighting a promising direction for enhancing cancer treatment. Finally, we discuss the critical challenges and barriers that must be addressed to push this emerging field toward clinical translation.