Cuproptosis: Advances in Stimulus‐Responsive Nanomaterials for Cancer Therapy

Cuproptosis, a recently identified non-apoptotic programmed cell death modality, attracts considerable attention in the realm of cancer therapeutics owing to its unique cellular demise mechanisms. Since its initial report in 2022, strategies inducing or amplifying cuproptosis for cancer treatment emerge. The engineering of nano-systems to elicit cuproptosis effectively circumvents constraints associated with conventional small-molecule pharmaceutical interventions, presenting novel prospects for oncological therapy. Stimulus-responsive nanomaterials, leveraging their distinctive spatiotemporal control attributes, are investigated for their role in modulating the induction or augmentation of cuproptosis. In this comprehensive review, the physiological characteristics of cuproptosis, encompassing facets such as copper overload and depletion, coupled with regulatory factors intrinsic to cuproptosis, are expounded upon. Subsequently, design methodologies for stimulus-responsive induction or enhancement of cuproptosis, employing stimuli such as light, ultrasound, X-ray, and the tumor microenvironment, are systematically delineated. This review encompasses intricacies in nanomaterial design, insights into the therapeutic processes, and the associated advantages. Finally, challenges inherent in stimulus-responsive induction/enhancement of cuproptosis are deliberated upon and prospective insights into the future trajectory of copper-mediated cancer therapy are provided.