Nanoparticle-induced ferroptosis: detection methods, mechanisms and applications

Although ferroptosis is an iron-dependent cell death mechanism involved in the development of some severe diseases (e.g., Parkinsonian syndrome, stroke and tumours), the combination of nanotechnology with ferroptosis for the treatment of these diseases has attracted substantial research interest. However, it is challenging to differentiate nanoparticle-induced ferroptosis from other types of cell deaths (e.g., apoptosis, pyroptosis, and necrosis), elucidate the detailed mechanisms and identify the key property of nanoparticles responsible for ferroptotic cell deaths. Therefore, a summary of these aspects from current research on nano-ferroptosis is important and timely. In this review, we endeavour to summarize some convincing techniques that can be employed to specifically examine ferroptotic cell deaths. Then, we discuss the molecular initiating events of nanosized ferroptosis inducers and the cascade signals in cells, and therefore elaborate the ferroptosis mechanisms. Besides, the key physicochemical properties of nano-inducers are also discussed to acquire a fundamental understanding of nano-structure-activity relationships (nano-SARs) involved in ferroptosis, which may facilitate the design of nanomaterials to deliberately tune ferroptosis. Finally, future perspectives on the fundamental understanding of nanoparticle-induced ferroptosis and its applications are provided.