巨细胞重编程通过调节未折叠的蛋白质响应与siRNA加载的磁纳米粒子在一个TAM类似的实验模型
Annarita D'Urso1, Francesca Oltolina1, Chiara Borsotti1
1Department of Health Sciences, School Medicine, Università del Piemonte Orientale A. Avogadro, Via Solaroli 17, 28100 Novara, Italy.
Pharmaceutics
|June 28, 2023
概括
新的纳米技术重新教育与瘤相关的巨细胞 (TAMs) 来对抗癌症. 携带siRNA的聚多巴胺合磁石纳米粒子 (PDA-MNPs) 抑制PERK,将TAM转移到一种用于新型癌症免疫治疗的抗瘤M1表型.
科学领域:
- 生物医学工程 生物医学工程
- 癌症研究 癌症研究
- 免疫学 免疫学 免疫学
背景情况:
- 与瘤相关的巨细胞 (TAMs) 在癌症进展中起着关键作用.
- TAMs在内分泌网膜 (ER) 中表现出不规则的未折叠蛋白质反应 (UPR),以生存压力.
- 从M2转向M1表型的TAM再极化是一种有前途的癌症免疫治疗策略.
研究的目的:
- 开发纳米技术来调节TAM的UPR.
- 研究与siRNA准PERK (siPERK) 功能化的聚多巴胺合磁纳米粒子 (PDA-MNPs).
- 为了评估PDA-MNPs/siPERK用于TAM再极化疗法.
主要方法:
- 开发了使用siPERK功能化的PDA-MNP.
- 在TAM类巨细胞 (PEMs) 中评估了细胞相容性,细胞吸收和基因沉默效率.
- 分析了M2巨细胞对M1表型的体外再极化.
主要成果:
- PDA-MNPs/siPERK显示了细胞兼容性和有效的细胞吸收.
- 证实了PERK表达的有效下调.
- 巨细胞通过抑制PERK.成功地被重新教育到M1表型.
结论:
- PDA-MNP是通过PERK抑制调节TAM的有效工具.
- 这种纳米技术为TAM向癌症免疫治疗提供了一个新的策略.
- 将TAM重新偏向到M1表型,为癌症治疗提供了潜在的新途径.
相关概念视频
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...