Department of Pharmacy, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
J Mater Chem B. 2021 Nov 24;9(45):9262-9284. doi: 10.1039/d1tb01289d.
Ferroptosis, a cell death pathway involving iron-related generation of lipid hydroperoxides for achieving incredible tumor suppression, has reignited the hope of chemotherapy in tumor treatment in the past decade. With extensive research studies, various bioactive proteins and cellular pathways have been demonstrated to regulate the occurrence and development of ferroptosis. The gradually established ferroptotic regulatory network is conducive to find effective proteins from a holistic perspective and guides better designs for future ferroptotic tumor therapies. The first section of this review summarizes the recent advances in ferroptotic regulatory mechanisms of proteins and attempts to clarify their latent function in the ferroptotic regulatory network. Second, the existing protein-mediated ferroptotic tumor nanotherapeutic strategies were reviewed, including the protein-mediated iron supplement, cell membrane transporter inhibition, glutathione peroxidase 4 interference, glutathione depletion, bioenzyme-mediated reactive oxygen species generation, heat shock protein inhibition, and tumor-overexpressed protein-triggered drug release for ferroptotic therapy. Finally, the future expectations and challenges of ferroptotic tumor nanotherapeutics for clinical cancer therapy are highlighted.
铁死亡是一种涉及铁相关的脂质过氧化物生成的细胞死亡途径，为肿瘤治疗中的化疗带来了新的希望。在过去的十年中，广泛的研究表明，各种生物活性蛋白和细胞途径调节铁死亡的发生和发展。逐渐建立的铁死亡调控网络有助于从整体角度寻找有效的蛋白，并指导未来铁死亡肿瘤治疗的更好设计。本文综述的第一部分总结了蛋白铁死亡调控机制的最新进展，并试图阐明其在铁死亡调控网络中的潜在功能。其次，综述了现有的蛋白介导的铁死亡肿瘤纳米治疗策略，包括蛋白介导的铁补充、细胞膜转运体抑制、谷胱甘肽过氧化物酶 4 干扰、谷胱甘肽耗竭、生物酶介导的活性氧生成、热休克蛋白抑制以及肿瘤过表达蛋白触发的铁死亡治疗药物释放。最后，强调了铁死亡肿瘤纳米治疗在临床癌症治疗中的未来期望和挑战。
