A high catalytic efficiency associated to a robust chemical structure are among the ultimate goals when developing new biocatalytic systems for biosensing applications. To get ever closer to these goals, we report here on a combination of metal-organic framework (MOF)-based nanozymes and G-quadruplex (G4)-based catalytic system known as G4-DNAzyme. This approach aims at combining the advantages of both partners (chiefly, the robustness of the former, the modularity of the latter). To this end, we used MIL-53(Fe) MOF and linked it covalently to a G4-forming sequence (F3TC), itself covalently linked to its cofactor hemin. The resulting complex (referred to as MIL-53(Fe)/G4-hemin) exhibited exquisite peroxidase-mimicking oxidation activity and an excellent robustness (being stored in water for weeks). These properties were exploited to devise a new biosensing system, based on a cascade of reactions catalyzed by the nanozyme (ABTS oxidation) and an enzyme, the alkaline phosphatase (or ALP, ascorbic acid 2-phosphate dephosphorylation). The product of the latter poisoning the former, we thus designed a biosensor for ALP (a marker of bone diseases and cancers), with a very low limit of detection (LOD, 0.02 U L -1 ) which is operative in human plasma samples.

Biocatalytic transformations in living cells, such as enzymatic cascades, function effectively in spatially confined microenvironments. However, mimicking enzyme catalytic cascade processes is challenging. Herein, we report a new dual-Hemin-Gquadruplex (dHemin-G4) DNAzyme with high catalytic activity over noncovalent G4/Hemin and monocovalent counterparts (G4-Hemin and Hemin-G4) by covalently linking hemin to both ends of an intramolecular G4. We use MAF-7, a hydrophilic metal− organic framework (MOF), as the protecting scaffold to integrate a biocatalytic cascade consisting of dHemin-G4 DNAzyme and glucose oxidase (GOx), by a simple and mild method with a single-step encapsulation of both enzymes. Such a MAF-7-confined cascade system shows superior activity over not only traditional G4/Hemin but also other MOFs (ZIF-8 and ZIF-90), which was mainly attributed to high-payload enzyme packaging. Notably, the introduction of hydrophilic G4 allows to avoid the accumulation of hydrophobic hemin on the surface of MAF-7, which decreases cascade biocatalytic activity. Furthermore, MAF-7 as protective coatings endowed the enzyme with excellent recyclability and good operational stability in harsh environments, including elevated temperature, urea, protease, and organic solvents, extending its practical application in biocatalysis. In addition, the incorporated enzymes can be replaced on demand to broaden the scope of catalytic substrates. Taking advantages of these features, the feasibility of dHemin-G4/GOx@MAF-7 systems for biosensing was demonstrated. This study is conducive to devise efficient and stable enzyme catalytic cascades to facilitate applications in biosensing and industrial processes.

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Given the complexity of the tumor microenvironment, multiple strategies are being explored to tackle hypoxic tumors. The most efficient strategies combine several therapeutic modalities and typically requires the development of multifunctional nanocomposites through sophisticated synthetic procedures. Herein, the G‐quadruplex (G4)‐forming sequence AS1411‐A (d[(G2T)4TG(TG2)4A]) is used for both its anti‐tumor and biocatalytic properties when combined with hemin, increasing the production of O2 ca. two‐fold as compared to the parent AS1411 sequence. The AS1411‐A/hemin complex (GH) is grafted on the surface and pores of a core‐shell upconverted metal‐organic framework (UMOF) to generate a UMGH nanoplatform. Compared with UMOF, UMGH exhibits enhanced colloidal stability, increased tumor cell targeting and improved O2 production (8.5‐fold) in situ. When irradiated by near‐infrared (NIR) light, the UMGH antitumor properties are bolstered by photodynamic therapy (PDT), thanks to its ability to convert O2 into singlet oxygen (1O2). Combined with the antiproliferative activity of AS1411‐A, this novel approach lays the foundation for a new type of G4‐based nanomedicine.