DNA Self-Assembly Generated by Aptamer-Triggered Rolling Circle Amplification Cascades for Profiling Colorectal Cancer-Derived Small Extracellular Vesicles

IF 15.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY ACS Nano Pub Date : 2025-01-07 DOI:10.1021/acsnano.4c12286

Yawei Feng, Yunshan Yang, Pei Guo, Lizhuan Zhang, Yunben Yang, Zeyin Zhao, Cheng Cui, Qiuxia Yang, Yong Liu, Liu Yang, Ruizi Peng, Weihong Tan

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Abstract

The analysis of small extracellular vesicles (sEVs) has shown clinical significance in early cancer diagnostics and considerable potential in prognostic assessment and therapeutic monitoring, offering possibilities for precise clinical intervention. Despite recent diagnostic progress based on blood-derived sEVs, the inability to specifically profile multiple parameters of sEVs proteins has hampered advancement in clinical applications. Herein, we report an approach to profile colorectal cancer (CRC)-derived sEVs by using multiaptamer-triggered rolling circle amplification (RCA) cascades. In practice, in the presence of target sEVs, the complementary strands are released from the duplexes of the structure-switching aptamer. Then, the RCA cascade occurs but only when the specific DNA strand pair is presented. As a result, the noncanonical DNA assemblies are generated whose size reaches micrometers that can be directly analyzed by conventional flow cytometry, thereby facilitating facile clinical diagnostics. In this study, the developed diagnostic method is verified on cell-derived sEVs, followed by achieving modeling based on clinical samples. The final diagnostic results from the clinical cohort indicate promising diagnostic efficacy for CRC-derived sEVs with 92% sensitivity, 86.7% specificity, and 90% overall accuracy, highlighting the substantial potential of sEVs as biomarkers for CRC diagnosis and significantly advancing the development of clinical tools for early disease diagnosis.

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由适体触发的滚动圈扩增级联产生的DNA自组装用于分析结直肠癌衍生的细胞外小泡

细胞外小囊泡（sev）的分析在早期癌症诊断中具有重要的临床意义，在预后评估和治疗监测中具有相当大的潜力，为精确的临床干预提供了可能。尽管最近基于血源性sev的诊断取得了进展，但无法特异性分析sev蛋白的多个参数阻碍了临床应用的进展。在此，我们报告了一种利用多适体触发的滚动环扩增（RCA）级联分析结直肠癌（CRC）衍生sev的方法。实际上，在目标sev存在的情况下，互补链从结构切换适配体的双链体中释放出来。然后，RCA级联发生，但只有当特定的DNA链对出现时。因此，产生的非典型DNA组装的大小达到微米，可以通过传统的流式细胞术直接分析，从而促进临床诊断。在本研究中，开发的诊断方法在细胞衍生的sev上进行验证，然后实现基于临床样本的建模。临床队列的最终诊断结果表明，基于CRC的sev具有良好的诊断效果，灵敏度为92%，特异性为86.7%，总体准确性为90%，突出了sev作为CRC诊断生物标志物的巨大潜力，并显著推动了早期疾病诊断临床工具的发展。

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来源期刊

ACS Nano 工程技术-材料科学：综合

CiteScore

26.00

自引率

4.10%

发文量

1627

审稿时长

1.7 months

期刊介绍： ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.