新型碳量子点通过抗氧化抑制协同纳米催化活性精确触发癌细胞中的铁死亡。
Novel Carbon Quantum Dots Precisely Trigger Ferroptosis in Cancer Cells through Antioxidant Inhibition Synergistic Nanocatalytic Activity.
发表日期:2024 Jul 15
作者:
Nianqiang Jin, Zilin Wang, Chengcheng Yin, Wenhuan Bu, Nuo Jin, Lingling Ou, Wenqiang Xie, Jiankang He, Xuan Lai, Longquan Shao
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
高水平的谷胱甘肽(GSH)是恶性肿瘤的重要特征,也是治疗无效和多重耐药的重要原因。尽管活性氧(ROS)疗法已被证明可以诱导肿瘤细胞死亡,但GSH对ROS的强烈清除作用显着降低了其治疗效果。因此,需要制定针对 GSH 的新策略。在这项研究中,设计并合成了源自庆大霉素的新型碳量子点(GM-CQD)。根据所得结果,GM-CQD含有sp2和sp3碳原子以及氮氧基团,通过下调SLC7A11降低细胞内GSH水平,从而破坏氧化还原平衡,介导脂质过氧化并诱导铁死亡。转录组分析表明,GM-CQD 下调与 GSH 代谢相关的分子表达,同时显着增加与铁死亡相关的分子表达。体内结果表明,GM-CQDs表现出优异的抗肿瘤活性和免疫激活能力。此外,由于其理想的生物安全性,GM-CQDs非常有希望作为靶向GSH的药物用于治疗恶性肿瘤。
High levels of glutathione (GSH) are an important characteristic of malignant tumors and a significant cause of ineffective treatment and multidrug resistance. Although reactive oxygen species (ROS) therapy has been shown to induce tumor cell death, the strong clearance effect of GSH on ROS significantly reduces its therapeutic efficacy. Therefore, there is a need to develop new strategies for targeting GSH. In this study, novel carbon quantum dots derived from gentamycin (GM-CQDs) were designed and synthesized. On the basis of the results obtained, GM-CQDs contain sp2 and sp3 carbon atoms as well as nitrogen oxygen groups, which decrease the intracellular levels of GSH by downregulating SLC7A11, thereby disrupting redox balance, mediating lipid peroxidation, and inducing ferroptosis. Transcriptome analysis demonstrated that GM-CQDs downregulated the expression of molecules related to GSH metabolism while significantly increasing the expression of molecules related to ferroptosis. The in vivo results showed that the GM-CQDs exhibited excellent antitumor activity and immune activation ability. Furthermore, because of their ideal biological safety, GM-CQDs are highly promising for application as drugs targeting GSH in the treatment of malignant tumors.