湖南大学Guosheng Song团队近期取得重要工作进展，他们研究提出了通过自由基链转移反应增强脂质过氧化在MRI引导下有效治疗小鼠肿瘤的策略。相关研究成果2023年12月19日在线发表于《科学通报》杂志上。

据介绍，脂质过氧化（LPO）是膜脂质氧化的过程，是癌症治疗中潜在的新细胞死亡形式。然而，LPO中涉及的自由基链式反应由起始、传播（最慢的步骤）和终止阶段组成，限制了其在体内的有效性。

为了解决这一局限性，研究人员将自由基链转移反应引入LPO过程，以靶向传播步骤，克服脂质过氧化速率缓慢的问题，从而促进内源性脂质过氧化，提高治疗效果。首先，合成了自由基链转移剂（CTA-1）/Fe纳米粒子（CTA-Fe-NPs-1）。CTA-1将低活性过氧自由基（ROO·）转化为高活性烷氧基自由基（RO·），产生自由基氧化循环，并增加脂质过氧化的传播。

此外，CTA-1/Fe离子增强活性氧（ROS）的产生，消耗谷胱甘肽（GSH），从而使GPX-4失活，促进自由基反应的起始阶段并减少自由基反应终止。CTA-Fe NPs-1诱导脂质膜中多不饱和脂肪酸的过氧化水平更高，导致癌症细胞的高效治疗。

此外，CTA-Fe-NPs-1可富集于诱导有效肿瘤抑制的肿瘤中，并表现出可激活的磁共振成像T₁-MRI对比度。

总之，CTA-Fe-NPs-1可以通过加速起始、传播和抑制终止步骤来增强细胞内脂质过氧化，促进自由基反应的循环，从而在荷瘤小鼠中产生有效的抗癌效果。

附：英文原文

Title: Enhancing lipid peroxidation via radical chain transfer reaction for MRI guided and effective cancer therapy in mice

Author: anonymous

Issue&Volume: 2023/12/19

Abstract: Lipid peroxidation (LPO), the process of membrane lipid oxidation, is a potential new form of cell death for cancer treatment. However, the radical chain reaction involved in LPO is comprised of the initiation, propagation (the slowest step), and termination stages, limiting its effectiveness in vivo. To address this limitation, we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation, thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes. Firstly, radical chain transfer agent (CTA-1)/Fe nanoparticles (CTA-Fe NPs-1) was synthesized. Notably, CTA-1 convert low activity peroxyl radicals (ROO·) into high activity alkoxyl radicals (RO·), creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation. Additionally, CTA-1/Fe ions enhance reactive oxygen species (ROS) generation, consume glutathione (GSH), and thereby inactivate GPX-4, promoting the initiation stage and reducing termination of free radical reaction. CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes, leading to highly effective treatment in cancer cells. In addition, CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging. In summary, CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation, propagation, and inhibiting termination step, promoting the cycle of free radical reaction, resulting in effective anticancer outcomes in tumor-bearing mice.

DOI: 10.1016/j.scib.2023.12.036

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927323009076