通过使用siRNA涂层的金属有机框架,克服增强免疫透的矩阵障碍
Cheng Zeng1, Xiaojing Chen2, Mingxi Lin1
1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Acta biomaterialia
|March 7, 2025
概括
我们开发了一种双受体向的纳米载体,以破坏瘤细胞外基质 (ECM) 屏障. 这种方法增强了免疫细胞的透,并抑制了三阴性乳腺癌 (TNBC) 的生长,为癌症免疫治疗提供了新的策略.
科学领域:
- 生物医学工程 生物医学工程
- 癌症生物学 癌症生物学
- 纳米技术纳米技术
背景情况:
- 瘤细胞外基质 (ECM) 形成物理屏障,阻碍免疫细胞的透,并导致免疫疗法耐药性,特别是在三阴性乳腺癌 (TNBC) 中.
- 迪斯科伊丁域受体2 (DDR2) 和整合素是调节ECM的关键受体,并与T细胞排除和TNBC治疗结果不佳有关.
研究的目的:
- 开发一种双受体向的纳米载体系统,用于输送siRNA来破坏TNBC中的ECM屏障.
- 调查同时向DDR2和整合素α-v (ITGAV) 的有效性,以增强抗瘤免疫力.
主要方法:
- 开发载有DDR2特异性siRNA (siDDR2) 和ITGAV特异性siRNA (siITGAV) 的金属有机框架 (MOF).
- 将MOF@siDDR2+siITGAV复合物给TNBC模型,以评估ECM调制和免疫细胞透.
- 评估原沉积,CD8+ T细胞透,编程细胞死亡联体1 (PD-L1) 表达和瘤生长抑制.
主要成果:
- 双向的MOF纳米载体显著减少了瘤微环境中的原体沉积.
- 治疗导致CD8+ T细胞的透增强,并抑制了编程细胞死亡配体1 (PD-L1) 的表达.
- 在TNBC模型中观察到显著的瘤生长抑制.
结论:
- 基于MOF的双受体向纳米载体有效地重编程瘤ECM以改善免疫细胞的可访问性.
- 这一策略通过克服物理障碍和增强抗瘤免疫反应,为协同癌症免疫疗法提供了一个有希望的方法.
- 调节ECM的机械特性是改善癌症治疗结果的创新策略.
相关概念视频
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
02:30Small interfering RNAs (siRNA)
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...