活细胞内同步降解circRNA <italic style="font-style: italic">CDR1as</italic>并实时监测miR-7的双功能纳米平台

黄艳; 叶佳琳; 许岚; 胡兴杰; 陈楠

doi:10.1631/jzus.B2500787

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活细胞内同步降解circRNA CDR1as并实时监测miR-7的双功能纳米平台

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Research Article | Updated：2026-07-29

活细胞内同步降解circRNA CDR1as并实时监测miR-7的双功能纳米平台
Dual-functional nanoplatform for simultaneous degradation of circRNA CDR1as and real-time monitoring of miR-7 in live cells
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2026年27卷第7期页码：761-774
Affiliations：

1.College of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Shanghai Engineering Research Center of Green Energy Chemical Engineering, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai 200234, China
2.School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 201318, China
Funds：

the Natural Science Foundation of Shanghai(24ZR1455600);the National Natural Science Foundation of China(21974089)
DOI：10.1631/jzus.B2500787
中图分类号：
CSTR：
收稿：2025-12-01，

修回：2026-04-08，

网络首发：2026-07-29，

纸质出版：2026-07-15
Accepted：

黄艳,叶佳琳,许岚等.活细胞内同步降解circRNA CDR1as并实时监测miR-7的双功能纳米平台[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(07):761-774.

Yan HUANG, Jialin YE, Lan XU, et al. Dual-functional nanoplatform for simultaneous degradation of circRNA CDR1as and real-time monitoring of miR-7 in live cells[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(7): 761-774. DOI: 10.1631/jzus.B2500787.
黄艳,叶佳琳,许岚等.活细胞内同步降解circRNA CDR1as并实时监测miR-7的双功能纳米平台[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(07):761-774. DOI： 10.1631/jzus.B2500787.

Yan HUANG, Jialin YE, Lan XU, et al. Dual-functional nanoplatform for simultaneous degradation of circRNA CDR1as and real-time monitoring of miR-7 in live cells[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(7): 761-774. DOI: 10.1631/jzus.B2500787. DOI：

摘要

环状RNA（circRNA）作为关键的转录后调控因子，在疾病发生发展中扮演着重要角色。然而，目前仍缺乏在活细胞层面对其进行精准操控与功能分析的有效工具。其中，circRNA

CDR1as

通过充当微小RNA-7（miR-7）的“分子海绵”，成为极具潜力的治疗靶标。本研究构建了一种基于沸石咪唑酯骨架-8（ZIF-8）金属有机框架的多功能纳米平台，以实现对

CDR1as

/miR-7调控轴的双重干预和动态监测。该纳米系统（DZ/MB@ZIF-8）同时负载了特异性切割

CDR1as

的脱氧核酶（DNAzyme）和监测miR-7水平的分子信标（MB）探针。纳米颗粒被细胞内吞并转运至溶酶体后，酸性环境触发载体分解，同步释放治疗组分与传感元件，并原位提供DNAzyme活性必需的Zn²⁺辅因子。实验结果表明，该平台能有效降解

CDR1as

，释放被捕获的miR-7，并显著抑制下游致癌基因表达。值得注意的是，治疗效应与MB探针产生的“信号开启型”荧光呈现高度正相关性，首次实现了在活细胞内对circRNA调控网络的实时可视化追踪。综上所述，这项工作构建了基因靶向治疗与内源生物传感协同作用的普适性诊疗体系，为circRNA功能研究和RNA靶向治疗开发提供了创新技术平台。

Abstract

Circular RNAs (circRNAs) are key post-transcriptional regulators with critical roles in pathogenesis

yet existing tools for their precise manipulation and functional analysis in living cells remain to be developed. A compelling therapeutic target in this field is the circRNA cerebellar degeneration-related protein 1 antisense (

CDR1as

)

functioning as an oncogenic sponge for microRNA-7 (miR-7). Herein

we report a novel multifunctional zeolitic imidazolate framework-8 (ZIF-8)-based nanoplatform for the simultaneous disruption and real-time monitoring of the

CDR1as

/miR-7 regulatory axis. This system

named DZ/MB@ZIF-8

co-encapsulates a designed set of DNAzymes (DZs) for the catalytic cleavage of

CDR1as

as well as a molecular beacon (MB) for reporting on miR-7 activity. Following cellular uptake and lysosomal trafficking

the acidic microenvironment triggers nanoplatform disassembly

concurrently releasing the therapeutic and sensing components along with essential Zn

cofactors for DZ activation. This system demonstrates efficient

CDR1as

degradation

which liberates miR-7 and inhibits the expression of its downstream oncogenic targets. Crucially

this therapeutic effect is directly correlated with a turn-on fluorescent signal from the MB

enabling the real-time

live-cell readout of circRNA regulation. This work establishes a versatile theranostic strategy that merges targeted gene regulation with intrinsic biosensing

offering a powerful platform for probing circRNA function and advancing RNA-based therapeutics.

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references

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活细胞内同步降解circRNA CDR1as并实时监测miR-7的双功能纳米平台

Dual-functional nanoplatform for simultaneous degradation of circRNA CDR1as and real-time monitoring of miR-7 in live cells

DOI：10.1631/jzus.B2500787

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Abstract

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