Bioorthogonal Disassembly of Hierarchical DNAzyme Nanogel for High-Performance Intracellular microRNA Imaging

Rolling circle amplification (RCA) enables the facile construction of compact and versatile DNA nanoassemblies which are yet rarely explored for intracellular analysis. This is might be ascribed to the uncontrollable and inefficient probe integration/activation. Herein, by encoding with tandem allosteric deoxyribozyme (DNA-cleaving DNAzyme), a multifunctional RCA nanogel was established for realizing the efficient intracellular microRNA imaging via the successive activation of the RCA-disassembly module and signal amplification module. The endogenous microRNA stimulates the precise degradation of DNA nanocarriers, thus leading to the efficient exposure of RCA-entrapped DNAzyme biocatalyst for an amplified readout signal. Our bioorthogonal DNAzyme disassembly strategy achieved the robust analysis of intracellular biomolecules, thus showing more prospects in clinical diagnosis.

Automated summary

Rolling circle amplification (RCA) is used to construct compact and versatile DNA nanoassemblies, but it is rarely used for intracellular analysis due to uncontrollable and inefficient probe integration/activation. Here, we developed a multifunctional RCA nanogel encoded with tandem allosteric deoxyribozyme for efficient intracellular microRNA imaging. The endogenous microRNA stimulates the precise degradation of DNA nanocarriers, leading to the exposure of RCA-entrapped DNAzyme biocatalyst for amplified readout signal. Our bioorthogonal DNAzyme disassembly strategy enables robust analysis of intracellular biomolecules with potential applications in clinical diagnosis.