Metal–Organic Framework-Loaded Engineering DNAzyme for the Self-Powered Amplified Detection of MicroRNA

Abstract

DNAzyme shows great promise in designing a highly sensitive and specific sensing platform; however, the low cellular uptake efficiency, instability, and especially the insufficient cofactor supply inhibit the intracellular molecule sensor applications. Herein, we demonstrate a novel type of DNAzyme-based self-driven intracellular sensor for microRNA (miRNA) detection in living cells. The sensor consists of a metal–organic framework [zeolite imidazole framework (ZIF-8)] core loaded with a shell consisting of a rationally designed DNAzyme, where the substrate strand is modified with FAM and BHQ-1 nearby both the sides of the restriction site, respectively, while the enzyme strand consists of two separate strands with a complementary fragment to the substrate strand and the targeting miRNA, respectively. The ZIF-8 nanoparticles enable the efficient delivery of DNAzyme into the cell and protect the DNAzyme from degradation. The pH-responsive ZIF-8 degradation is accompanied with the release of the DNAzyme and Zn2+ cofactors, and the intracellular target miRNAs recognize and activate the DNAzyme driven by the Zn2+ cofactors to cleave the substrate strand, resulting in the release of the FAM-labeled shorter product strand and increased fluorescence for miRNA detection. The self-driven approach can be generally applied to various miRNAs’ detection through DNAzyme engineering.

Metal–organic framework-derived photoelectrochemical sensors: structural design and biosensing technology

“…For intracellular microRNA (miRNA) detection, Su et al designed the complexes (ZIF-8@DNAzyme) by combining DNAzyme with ZIF-8 to generate fluorescence intracellularly. 93 The DNAzyme, which is a complementary fragment of the target miRNA complementarily, pairs with the substrate strand modified by the fluorescent tags. Through the electrostatic interaction, ZIF-8 binds tightly to DNAzyme and forms an annular catalytic domain to protect DNAzyme from loop breaking and drive the substrate strand breakage.…”

Tunable metal–organic frameworks assist in catalyzing DNAzymes with amplification platforms for biomedical applications

“…There were many studies on screening Dzs and improving detection sensitivity through specific modification of Dzs. [179][180][181] An outstanding study has developed a microRNA-21 electro-chemiluminescence biosensor based on Co-Ti 3 C 2 composites and double-stranded specific nucleaseassisted signal amplification. 16 Porphyrin MOFs as an electrochemical probe for DNA sensing via a triple helix molecular switch, combined with DNA recirculation amplification, significantly improved the sensitivity of the biosensor.…”

“…68,200,249,251,252 Molecular detection of solid tumors makes precision treatment possible, while micro-robots achieve precision treatment of tumors due to micro-invasion and precise control. 181…”

RNA-cleaving DNAzymes for accurate biosensing and gene therapy

“…3C). 60 The DNAzymes are driven by Zn 2+ to cleave the substrate strand for fluorescently imaging intercellular miRNA. Similarly, Li et al investigated a light-activated walker consisting of a dissociable ZIF-8 for ensuring sufficient internal cofactors (Zn 2+ ) to facilitate the detection of miRNA in living cells.…”