Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry , Wuhan University , Wuhan 430072 , PR China.
ACS Nano. 2018 Dec 26;12(12):12181-12192. doi: 10.1021/acsnano.8b05860. Epub 2018 Nov 26.
Non-apoptotic ferroptosis is of clinical importance because it offers a solution to the inevitable biocarriers of traditional apoptotic therapeutic means. Inspired by industrial electro-Fenton technology featured with electrochemical iron cycling, we construct ferrous-supply-regeneration nanoengineering to intervene tumorous iron metabolism for enhanced ferroptosis. Fe ion and naturally derived tannic acid (TA) spontaneously form a network-like corona onto sorafenib (SRF) nanocores. The formed SRF@FeTA nanoparticles can respond to a lysosomal acid environment with corona dissociation, permitting SRF release to inhibit GPX4 enzyme for ferroptosis initiation. TA is arranged to chemically reduce the liberated and the ferroptosis-generated Fe to Fe, offering iron redox cycling to, thus, effectively produce lipid peroxide required in ferroptosis. Sustained Fe supply leads to long-term cytotoxicity, which is identified to be specific to HO-overloaded cancer cells but minimal in normal cells. SRF@FeTA-mediated cell death proves to follow the ferroptosis pathway and strongly inhibits tumor proliferation. Moreover, SRF@FeTA provides a powerful platform capable of versatile integration between apoptosis and non-apoptosis means. Typically, photosensitizer-adsorbed SRF@FeTA demonstrates rapid tumor imaging owing to the acid-responsive fluorescence recovery. Together with ferroptosis, imaging-guided photodynamic therapy induces complete tumor elimination. This study offers ideas about how to advance anticancer ferroptosis through rational material design.
非凋亡性铁死亡具有重要的临床意义，因为它为传统凋亡治疗手段所不可避免的生物载体提供了一种解决方案。受具有电化学铁循环特点的工业电芬顿技术启发，我们构建了铁供应再生纳米工程，以干预肿瘤铁代谢，增强铁死亡。Fe 离子和天然来源的单宁酸（TA）自发地在索拉非尼（SRF）纳米核上形成网状冠。形成的 SRF@FeTA 纳米颗粒可以响应溶酶体酸性环境，发生冠状物解离，从而允许 SRF 释放以抑制 GPX4 酶，引发铁死亡。TA 被安排用于化学还原释放的和铁死亡产生的 Fe 为 Fe，提供铁氧化还原循环，从而有效地产生铁死亡所需的脂质过氧化物。持续的铁供应导致长期细胞毒性，这被确定为 HO 过负荷癌细胞特有的，但在正常细胞中最小。SRF@FeTA 介导的细胞死亡被证明遵循铁死亡途径，并强烈抑制肿瘤增殖。此外，SRF@FeTA 提供了一个强大的平台，能够在凋亡和非凋亡手段之间进行多功能整合。通常，吸附了光敏剂的 SRF@FeTA 由于酸响应荧光恢复而表现出快速的肿瘤成像。与铁死亡一起，成像引导的光动力疗法可完全消除肿瘤。本研究提供了关于如何通过合理的材料设计推进抗癌铁死亡的思路。
