脂质纳米颗粒代码传递系统通过铁 - 亡增强抗瘤效应与编程细胞死亡相结合 1 下调调节
Weiran Cao1, Xue Zhang1, Yaxuan Feng1
1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, International Joint Laboratory of Ocular Diseases, School of Pharmacy, School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China.
ACS nano
|June 13, 2024
概括
这项研究将一种谷氨抑制剂和化疗药物与一种免疫治疗剂结合起来,以克服癌症药物耐药性. 这种新的纳米粒子输送系统通过诱导铁亡,亡和增强适应性免疫力,有效地减少了瘤的生长.
科学领域:
- 生物医学工程 生物医学工程
- 癌症研究 癌症研究
- 纳米医学是一种纳米医学.
背景情况:
- 药物耐药性限制了癌症治疗的有效性,部分原因是抗氧化剂,如谷氨 (GSH) 中和化疗诱导的活性氧物种 (ROS).
- 克服这种抵抗需要策略来破坏细胞内氧化还原平衡,并增强药物诱导的细胞死亡.
- 将化疗与免疫调节剂结合起来可以改善抗瘤反应.
研究的目的:
- 开发一种多药纳米粒子系统,以克服癌症中的化疗耐药性.
- 为了同时诱导ferroptosis和apoptosis,同时提高抗瘤免疫力.
- 为了研究一种GSH抑制剂,ROS基药物和PD-L1阻断的协同效应.
主要方法:
- 埃拉斯 (GSH 抑制剂),FdUMP (基于ROS的药物) 和siPD-L1的同时使用GE11改性脂质纳米颗粒 (LNP) 与酸核.
- 在体外评估细胞毒性,ROS诱导,GSH/GPX4下调,脂质过氧化和线粒体脱极化.
- 在皮下结肠癌 (CRC) 鼠标模型中瘤抑制的体内评估.
主要成果:
- 这种LNP配方表现出增强的细胞毒性,并有效地破坏了氧化还原平衡.
- 观察到同时诱导ferroptosis和apoptosis,导致显著的脂质过氧化和线粒体损伤.
- 在体内研究表明,在有效瘤积累的CRC模型中,实质性瘤抑制 (高达83.89%).
结论:
- 开发的纳米粒子系统通过耗尽GSH并诱导细胞死亡,成功克服了耐药性.
- 结合PD-L1阻断的联合治疗通过激活自适应性免疫来协同增强抗瘤效应.
- 这一策略为提高癌症治疗疗效提供了一个有希望的方法.
相关概念视频
02:26Protein Networks
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:11Cellular Injury IlI: Cellular Death
Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...