通过氧化调节细胞应激反应以增强过载介导的瘤治疗
Xue Zhou1, Chencheng Gao2, Cuimei Liu1
1Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, PR China.
Biomaterials
|September 4, 2025
概括
我们开发了基于氨基酸的新型纳米粒子来治疗癌症. 这些L-阿基因/酸纳米颗粒诱导协同过载,增强亡并克服瘤细胞适应以改善治疗.
科学领域:
- 生物材料科学
- 纳米技术
- 癌症治疗方法
背景情况:
- 基于氨基酸 (AA) 的纳米粒子 (NP) 在癌症治疗中具有生物相容性和治疗潜力.
- 开发基于AA的NP的有效合成方法对于推进癌症治疗至关重要.
研究的目的:
- 开发一种通用的一步方法来合成基于AA的NP.
- 通过协同过载来设计L-素 (L-Arg) /酸 (CaP) 的NP来加强癌症治疗.
- 研究L-Arg/CaPNP诱导细胞亡和免疫细胞死亡的机制.
主要方法:
- 使用单步方法合成L-/酸纳米颗粒.
- 在酸性瘤微环境 (TME) 中评估NP降解和离子 (Ca2+) 释放.
- 研究L-Arg衍生的氧化物 (NO) 对细胞内Ca2+调节的影响,包括酸受体 (RyR) 的S-化和血膜Ca2+-ATPase (PMCA) 的下调.
- 在体外和体内研究以评估瘤抑制和生物安全性.
主要成果:
- 在TME中迅速降解L-Arg/ CaPNP,释放出大量的外源Ca2+.
- 通过促进ER Ca2+释放 (通过RyR S- 化) 和抑制Ca2+流出 (通过PMCA下调) 来调节L-Arg衍生的NO细胞内Ca2+.
- 一个三级调节机制放大了细胞内Ca2+度,克服了瘤细胞的适应.
- 在体外和体内表现出优异的生物安全性.
结论:
- 通过诱导协同过载,L-Arg/CaPNP代表了癌症的新疗法.
- 设计的NP有效地结合了过载和气体 (NO) 治疗,以增强抗癌效果.
- 这种方法通过克服传统治疗的局限性来建立癌症治疗的新范式.
相关概念视频
Nitric Oxide Signaling Pathway
5.2K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.2K
mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
Paracrine Signaling
55.7K
Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
55.7K
Drugs that Stabilize Microtubules
2.1K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
Adaptive Mechanisms in Cancer Cells
5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K


