Cuproptosis, a newly discovered copper-dependent mode of cell death, has received extensive attention in the field of cancer therapy due to its specific activation pathway. Rapid accumulation of large amounts of copper ions within the cancer cells to achieve copper overload is the key to activating cuproptosis. Advanced nanotechnology offers considerable promise for delivering ions to cancer cells, in which copper-based nanomaterials have been proposed to evoke cuproptosis-mediated cancer therapy. However, it is still a great challenge to induce copper overload specifically in tumors and efficiently activate subsequent cuproptosis-related molecular pathways. Therefore, it is necessary to summarize the strategies used to effectively activate or amplify cuproptosis based on currently developed copper-based nanomaterials, providing ideas for the design of nanomaterials in the future. In this review, copper-based nanomaterials that can be used to activate cuproptosis are systematically classified for nanomaterials selection. Subsequently, cuproptosis sensitization strategies using copper-based nanomaterials are provided to amplify the therapeutic efficiency. Meanwhile, cuproptosis-related combination therapies for maximizing treatment efficacy are delineated. Ultimately, the remaining challenges and feasible future directions in the use of cuproptosis for tumor therapy based on copper-based nanomaterials are also discussed.

Programmed cell death (PCD) is defined as regulated cell death controlled by an intracellular program. While apoptosis was once thought to be the only kind of PCD, current understanding has expanded to include other forms such as pyroptosis, autophagy, and necroptosis. These processes, especially apoptosis and necroptosis, serve as natural defenses that restrict cancer cells from surviving and disseminating. However, cancer cells have evolved various strategies to evade PCD, including genetic mutations and epigenetic modifications in key modulators of PCD pathways. With the continuous development of nanotechnology, emerging nanomaterials (NMs) are considered to break through this bottleneck due to their intrinsic physicochemical properties. Especially, new kinds of cell death induced by NMs, such as ferroptosis, cuproptosis, and calcium overload, show gratifying potential in cancer therapy, which is closely linked to the role of metal ions. Additionally, other metal ions-induced cell death such as sodium and zinc have also emerged in an endless stream. Hence, we propose the term “metalloptosis” to describe cell death induced by metal ions and summarize its application in cancer therapy through NMs. This review will delve into the critical design principles for engineering NMs involved in metalloptosis and provide a comprehensive summary of current metal ions-mediated cancer therapies, focusing on nanoplatforms and their mechanisms of action. We hope that this review will provide a new perspective on metal ions-mediated cancer therapy based on nanotechnology.

Organic afterglow luminescent probes (OALPs), characterized by their long-lasting luminescence after irradiation (by light, ultrasound, or X-rays) cessation, are pivotal tools in autofluorescence-free optical imaging. They exhibit ultra-low background noise interference, enhancing imaging sensitivity and ensuring clearer, more reliable imaging results. Moreover, they offer deeper tissue penetration compared to traditional optical imaging modalities, providing various information from deep tissues. Recently developed sonoafterglow and radioafterglow further enhance tissue penetration depth. This review outlines 2 design approaches for OALPs: coencapsulation and conjugation, which are derived from their luminescent mechanism. Guided by these strategies, researchers have designed 3 types of OALPs: near-infrared OALPs, responsive OALPs, and ratiometric OALPs. Additionally, we also provided examples of how OALPs are integrated with therapy and applied in the field of cancer theranostics. Finally, we discuss certain challenges encountered in the advancement of the next generation of OALPs, aiming to broaden their scope of applications.