通过DNA介导的自组装氧化损伤放大器与铜和MTH1抑制剂相结合,用于癌症治疗
Cui Ren1, Zhiyong Shi2, Xiaowen Zhang2
1Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, China.
Bioactive materials
|December 19, 2024
概括
工程纳米颗粒扩大氧化损伤,用于增强化学动力疗法 (CDT) 和基因疗法,通过克服谷氨防御和DNA修复机制,有效抑制瘤.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 癌症治疗 癌症治疗
背景情况:
- 化学动力疗法 (CDT) 通过产生反应性氧物种 (ROS) 来治疗瘤具有前景.
- 瘤细胞通过高谷氨 (GSH) 水平和像MTH1.1这样的ROS清除酶抵抗CDT.
- 现有的CDT方法由于这些防御机制而面临局限性.
研究的目的:
- 设计DNA介导的自组装纳米粒子 (HTCG@TA NPs) 来增强氧化损伤和协同抗瘤效应.
- 通过向GSH和MTH1.1,克服瘤对CDT的抵抗力.
- 将CDT与基因疗法结合起来,以增强瘤抑制.
主要方法:
- 通过DNA介导的自我组装合成了HTCG@TA NP.
- 铜离子 (Cu2+) 用于耗尽GSH并催化ROS (基基) 的产生.
- TH588被纳入,以抑制MTH1介导的DNA修复.
- 包括G3139,一种功能性核酸,用于降低Bcl-2表达的调节.
主要成果:
- 工程纳米粒子有效地耗尽了GSH,并增加了ROS水平.
- TH588释放抑制了MTH1,增强了氧化DNA损伤.
- G3139降低了Bcl-2的调节,促进了瘤细胞的亡.
- HTCG@TA NPs在体外和体内都表现出显著的瘤抑制.
结论:
- HTCG@TA NPs为协同化学动力学和基因治疗提供了一个新的纳米平台.
- 这种方法有效地放大氧化损伤,克服瘤抵抗机制.
- 这些发现为临床癌症治疗提供了一个有希望的新策略.
相关概念视频
Electron Transport Chain: Complex I and II
11.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
11.3K
DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K
Treatment Resistant Cancers
3.2K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
Targeted Cancer Therapies
7.4K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.4K
Mutations
33.7K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
33.7K


