Kusi Dipa, Sun Yan, Liu Chenguang
Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.
Department of Cardiology, Zhejiang Rongjun Hospital, Jiaxing 314001 PR China.
Int J Pharm. 2025 Jan 25;669:125101. doi: 10.1016/j.ijpharm.2024.125101. Epub 2024 Dec 18.
Ferroptosis, a regulated form of cell death distinct from apoptosis, was first identified in 2012 and is characterized by iron-dependent lipid peroxidation driven by reactive oxygen species (ROS). Since its discovery, ferroptosis has been linked to various diseases, with recent studies highlighting its potential in cancer therapy, particularly for targeting cancer cells that are resistant to traditional treatments like chemotherapy and radiotherapy. While iron has historically been central to ferroptosis, emerging evidence indicates that non-ferrous ions, especially manganese (Mn), also play a crucial role in modulating this process. Mn-based nanomaterials have shown significant promise in cancer treatment by enhancing ROS production, depleting antioxidant defenses, and inducing ferroptosis. Additionally, these materials offer advantages in tumor imaging, immunotherapy, and catalyzing the Fenton-like reactions essential for ferroptosis. This review delves into the mechanisms of Mn-induced ferroptosis, focusing on recent advancements in Mn-based nanomaterials and their applications in chemodynamic therapy and immunotherapy. By leveraging non-ferrous ion-mediated ferroptosis, these approaches provide a novel avenue for cancer treatment. Furthermore, this review explores the potential role of Mn-based nanomaterials in the lipid metabolism pathways involved in ferroptosis and highlights the advantages of Mn ions over other metals in promoting ferroptosis. These insights offer new perspectives for the development of tumor therapies centered on Mn-based nanomaterials.
铁死亡是一种不同于细胞凋亡的程序性细胞死亡形式，于2012年首次被发现，其特征是由活性氧（ROS）驱动的铁依赖性脂质过氧化。自发现以来，铁死亡已与多种疾病相关联，最近的研究突出了其在癌症治疗中的潜力，特别是针对对化疗和放疗等传统治疗有抗性的癌细胞。虽然铁一直是铁死亡的核心，但新出现的证据表明，有色金属离子，尤其是锰（Mn），在调节这一过程中也起着关键作用。基于锰的纳米材料通过增强ROS生成、消耗抗氧化防御和诱导铁死亡，在癌症治疗中显示出巨大的前景。此外，这些材料在肿瘤成像、免疫治疗以及催化铁死亡所必需的类芬顿反应方面具有优势。本综述深入探讨了锰诱导铁死亡的机制，重点关注基于锰的纳米材料的最新进展及其在化学动力疗法和免疫治疗中的应用。通过利用有色金属离子介导的铁死亡，这些方法为癌症治疗提供了一条新途径。此外，本综述探讨了基于锰的纳米材料在铁死亡相关脂质代谢途径中的潜在作用，并强调了锰离子在促进铁死亡方面相对于其他金属的优势。这些见解为以基于锰的纳米材料为中心的肿瘤治疗发展提供了新的视角。
