研究进展

经纳米线递送 miRNA 恢复衰老 T 细胞的功能应答

来源:Cell biomaterials · PMID 42979563 · DOI 10.1016/j.celbio.2026.100514 · 来源:IMA 知识库《文献层·文献监控卡片》2026-11-05 期 · 全文级(file_id dAlZBwueyWSz,实际下载核验 1,395,640 B) · 全文已获取并通过三重归属校验

时间标签:数据日期 2026-11-05 · 生成时间 2026-11-05 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 | 情报发生日期 2026-11-05

研究问题

We initially examined how the nanowire interfaces physically with aged and young T cells and whether it could access the cell interior.;These findings demonstrate that nanowires facilitate the delivery of miRNA to aged CD8+ T cells at levels comparable to those in young cells, which is an important factor for ex vivo programming of aged T cells.To determine whether nanowire-mediated uptake relies on traditional endocytic pathways, we used chemical inhibitors dynasore67 and chlorpromazine68 to block endocytosis and compared the delivery of 6-FAM-miR-29 via nanowires, nucleofection, Lipofectamine, and 2D culture.;Accordingly, we focused subsequent analyses on miR-29 mimic and miR-29-ASO as functionally informative regulators within this axis.We asked whether these baseline adjustments translate into altered early differentiation trajectories upon activation.

方法

Moreover, their cytocompatibility, scalable fabrication, and amenability to multiplexed functionalization position silicon nanowires as a broadly applicable platform for precision modulation of cell states, with implications for regenerative medicine, immunotherapy, and translational bioengineering.In this study, we employed PEI-functionalized nanowires to transiently enhance functional responses in aged murine CD8+ T cells through the programmable delivery of miRNA.;We initially established efficient, high-viability delivery in aged cells and demonstrated that specific single miRNA inputs can modulate the T cell transcriptome at baseline and sustain this modulation through early activation.;Building upon this finding, we implemented a multiplexed-miRNA cocktail comprising miR-29 antisense oligonucleotide (ASO), miR-130, miR-150, and miR-181a.

核心结论

We initially established efficient, high-viability delivery in aged cells and demonstrated that specific single miRNA inputs can modulate the T cell transcriptome at baseline and sustain this modulation through early activation.;Importantly, primary aged human CD8+ T cells programmed with the same single- and multiplexed miRNAs targeting transcriptional networks and signaling pathways governing T cell functions demonstrated consistent shifts toward early functional priming at both early and extended post-activation stages, without a concomitant rise in exhaustion phenotype following repeated stimulations.;We previously demonstrated that this geometry provides sufficient rigidity for cell interfacing while ensuring high viability and T cell health,66 as it prevents puncturing through the entire cell diameter.

局限

This observation should be interpreted in the context of subset composition.;Again, however, this should not be interpreted as evidence of a fully restored or permanently youthful transcriptional state.;Interestingly, however, young CD8+ T cells in this system demonstrated the highest absolute levels of IFN-γ and TNF-α.

对本项目的价值

中等价值:属「代谢 / 内分泌 / 肝肾老化」方向;代谢 / 内分泌 / 肝肾老化的界面栏目可用作本项目文献库与综述素材。 | 价值分 2.9/5(★★★☆☆)

全文来源

PubMed PMC JATS(正文 93,652 字符,题名指纹 0.89,已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验)

原文题录

  • 中文题名:经纳米线递送 miRNA 恢复衰老 T 细胞的功能应答
  • 英文标题:miRNA delivery via nanowires restores functional responses in aged T cells.
  • 期刊与标识:Cell biomaterials · PMID 42979563 · DOI 10.1016/j.celbio.2026.100514 · PMC PMC13730167

A 级证据分级:A 级(同行评议人体研究)

本文属人体研究证据,但需注意:观察性或小样本干预的结论不等于已证实临床获益;效应量与长期安全性仍需更大规模、更长随访的试验验证。

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