近日，湖南大学楚霞团队开了一种空间提示、顺序激活的DNA纳米装置，通过精确靶向病变巨噬细胞用于动脉粥样硬化治疗。相关论文于2026年2月24日发表在《美国化学会志》上。

动脉粥样硬化（AS）作为心血管疾病的主要诱因，其发病机制中巨噬细胞扮演关键驱动角色。开发既能有效缓解AS又能最大限度减少全身效应的巨噬细胞靶向疗法仍具挑战。

研究组提出了一种利用精准时空特异性响应DNA纳米结构（ASfindaCure）的智能诊疗方法。为实现对致动脉粥样硬化巨噬细胞的精准靶向，研究组利用其独特的空间表达模式，该模式包含膜蛋白（SIRPα）、微环境信号（凝血酶）以及两种细胞内生物标志物（APE1和微小RNA-155）。通过结构性和动态DNA纳米技术，ASfindaCure借助可编程反应离子级联，在时间上协调对这些空间分布生物标志物的识别事件。

利用荧光和光声双模态成像，研究组证实ASfindaCure能精准靶向致AS巨噬细胞，为评估AS进展提供了一种无创成像方法。在细胞和小鼠模型中，ASfindaCure展示了将microRNA-33反义寡核苷酸有效递送至靶细胞的能力，显著减缓了斑块进展和炎症。这种智能诊疗纳米平台为开发下一代AS疗法奠定了重要基础，并在其他疾病的治疗中具有潜在应用价值。

附：英文原文

Title: A Spatially Cued, Sequentially Activated DNA Nanodevice for Atherosclerosis Theranostics via Precise Targeting of Lesional Macrophages

Author: Ping Xie, Xumin Pan, Ruixi Peng, Siyuan Liu, Xixi Chen, Qiaomei Wei, Li-Juan Tang, Lan Liu, Jianhui Jiang, Xia Chu

Issue&Volume: February 24, 2026

Abstract: Atherosclerosis (AS), a major contributor to cardiovascular diseases, involves macrophages as a pivotal driver of its pathogenesis. Developing macrophage-targeted therapies that effectively mitigate AS while minimizing systemic effects remains a challenge. Here, we present an intelligent theranostic method for AS using an accurate spatiotemporal-specifically responsive DNA nanostructure (ASfindaCure). To precisely target atherogenic macrophages, we leverage a spatially distinctive expression pattern comprising a membrane protein (SIRPα), a microenvironmental cue (thrombin), and two intracellular biomarkers (APE1 and microRNA-155). By harnessing structural and dynamic DNA nanotechnologies, ASfindaCure temporally orchestrates recognition events for these spatially distributed biomarkers via programmable reactive ion cascades. Utilizing fluorescence and photoacoustic dual-modality imaging, we demonstrate that ASfindaCure accurately targets AS-causing macrophages, providing a noninvasive imaging method to assess AS progression. In both cellular and mouse models, ASfindaCure demonstrated effective delivery of microRNA-33 antisense oligonucleotides to targeted cells, significantly mitigating plaque progression and inflammation. This intelligent theranostic nanoplatform holds great promise for the development of next-generation treatments for AS and has potential applications in other disease conditions.

DOI: 10.1021/jacs.5c19539

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c19539