Liu Yang, Chen Jinzhu, He Zi, Luo Huiling, Liu Xinxin, Sun Yanan, Ge Dongtao, Liu Xin, Shi Wei
The Higher Educational Key Laboratory, for Biomedical Engineering of Fujian Province/Research Center of Biomedical Engineering of Xiamen, Xiamen Key Laboratory of Fire Retardant Materials/Fujian Provincial Key Laboratory of Fire Retardant Materials, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361005, China.
Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China.
Biomater Sci. 2023 Jan 17;11(2):542-553. doi: 10.1039/d2bm01172g.
Ferroptosis induced by iron-dependent accumulation of lipid peroxides (LPOs) has received increasing attention in cancer therapy, especially chemodynamic therapy (CDT). However, the quick annihilation of hydroxyl radicals (˙OH) severely restricts the ˙OH/LPO conversion efficiency, which has become one of the key factors that influences the therapeutic efficacy of ferroptosis-based CDT. Herein, we designed a ˙OH/LPO nano-converter with a high LPO generation efficiency loading ferrocene (Fc), a green Fenton catalyst, in the phospholipid bilayer of liposome-PEG (Fc-Lp-PEG). Under catalysis with Fc, the over-expressed HO in tumors can be decomposed to ˙OH. The generated ˙OH reacts with unsaturated lipids on the liposome, and is converted into LPOs, which spread the lipid peroxidation chain reaction to the remote membranes of cells and organelles, triggering efficient cancer cell ferroptosis. Systematic and therapeutic outcomes showed the high tumor inhibition ratio (74.0%) and the low side effects of Fc-Lp-PEG on 4T1 tumor-bearing mice. This novel strategy for improving the ˙OH/LPO conversion efficiency might provide new insights for the clinical development of ferroptosis-based CDT.
由脂质过氧化物（LPOs）的铁依赖性积累诱导的铁死亡在癌症治疗中受到越来越多的关注，尤其是在化学动力学疗法（CDT）中。然而，羟基自由基（˙OH）的快速湮灭严重限制了˙OH/LPO的转化效率，这已成为影响基于铁死亡的CDT治疗效果的关键因素之一。在此，我们设计了一种具有高LPO生成效率的˙OH/LPO纳米转换器，即在脂质体-聚乙二醇（Fc-Lp-PEG）的磷脂双层中负载二茂铁（Fc），一种绿色芬顿催化剂。在Fc的催化下，肿瘤中过表达的H2O2可分解为˙OH。生成的˙OH与脂质体上的不饱和脂质反应，并转化为LPOs，后者将脂质过氧化链反应扩散到细胞和细胞器的远端膜，触发高效的癌细胞铁死亡。系统和治疗结果显示，Fc-Lp-PEG对4T1荷瘤小鼠具有高肿瘤抑制率（74.0%）和低副作用。这种提高˙OH/LPO转化效率的新策略可能为基于铁死亡的CDT的临床开发提供新的见解。
