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 Zn²⁺ 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.

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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