Rational Design of a Dual-Layered Metal–Organic Framework Nanostructure for Enhancing the Cell Imaging of Molecular Beacons

Abstract

As the most popular nucleic acid probe, molecular beacons (MBs) can selectively light up endogenous RNA targets without specific treatment. However, the poor cell permeability and unsatisfied intracellular stability of MBs significantly restricted their detection performance. Herein, we report the encapsulation of MB within a dual-layered metal–organic framework nanostructure UiO66-ZIF8 for enhanced cell imaging. UiO66-NH2 nanoparticles were synthesized as the template for MB loading, and the ZIF-8 shell was further coated on the surface of UiO66-MB to ensure its stability and lysosomal escape effect. Taking multidrug-resistant (MDR1) mRNA as a model target, MBs loaded within UiO66-ZIF8 showed an improved lysosomal escape effect compared with MB absorbed on UiO66-NH2. Therefore, efficient and accurate intracellular MDR1 mRNA imaging was realized with UiO66-MB-ZIF8. This work presented a new method for the rational regulation of the intracellular fate of MOF-based nanoprobes and will facilitate the further development of hierarchical MOF nanoprobes for analytical applications.

Metal–Organic Framework Nanoparticles Power DNAzyme Logic Circuits for Aberrant MicroRNA Imaging

“…Recently, metal–organic frameworks (MOF NPs) have attracted great attention in selective catalysis, gas storage and separation, − and drug delivery − owing to their large surface area, high and tunable porosity, and good functionalization . In particular, zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs), a subclass of MOF NPs, have been utilized as a smart nanocarrier for accommodating functional nucleic acids containing siRNA, CpG, and DNAzyme by electrostatic interactions. − Moreover, the nanoscale ZIF-8 NPs can be delivered into cells via the endocytosis pathway and then decomposed under acidic conditions of endo-lysosomes to motivate the controlled cargo release. − Recent studies have found that Cu 2+ -doped ZIF-8 NPs (Cu/ZIF-8 NPs) not only maintain the unique properties of ZIF-8 NPs but also supplement an adequate amount of DNAzyme cofactor to implement the biocatalytic operation of the Cu 2+ -dependent DNAzyme in living cells. , Thus, the Cu/ZIF-8 NP-based nanoplatform could be employed as a versatile self-driven nanocarrier for the efficient delivery of DNAzyme logic circuits into cells.…”

Covalent Organic Framework-Based Spherical Nucleic Acid Probe with a Bonding Defect-Amplified Modification Strategy

“…SNAPs are novel nucleic acid structures employing nanoparticles as cores and dense nucleic acid as shells. − These nanostructures possess enhanced stability and better diagnostic and therapeutic performance. , For instance, compared with free nucleic acid molecules, the enzyme resistance effect of SNAPs is stronger. , SNAPs possess better cellular uptake effects, enabling efficient intracellular biomarker detection and drug delivery without the employment of transfection agents. − Therefore, a great number of counterparts based on diverse nanoparticles have been devised. − Similar to metal–organic frameworks, − COFs possess many attractive structural and functional characteristics, − COF-based SNAPs may be a new category of nanomaterials for theranostic applications. However, it is challenging to directly graft dense nucleic acid molecules onto COF NPs because not only there are limited connecting sites on COFs for the immobilization of the nucleic acid molecules but also the strong interaction between COF NPs and nucleic acid skeletons results in the random adsorption of these molecules onto COF NPs, making it hard to decorate the high density of nucleic acid molecules with the desired spatial arrangement to form SNAPs.…”

Advances in Nanoparticles for Effective Delivery of RNA Therapeutics

“…6a) [80]. In the case of delivering molecular beacons via Zr-based MOFs, selectively lighting up endogenous RNA targets have been shown by double-layer MOFs even without specific treatments [81]. Similarly, Liu et al investigated VEGF mRNA by monitoring MOFs under hypoxia in living cells.…”