Nanozyme engineering in structurally explicit framework: Design mechanisms and biosensing applications

Natural enzymes are crucial catalysts that not only control over the biotransformation in intracellular environments with high efficiency but also are widely harnessed in vitro for diverse applications, among which are used as a core element to engineer biosensor attributing to their high sensitivity and specificity in recognition. However, the vulnerable conformation of a native enzyme arises a series of unavoidable issues associated with lifetime and cost effectiveness, greatly limiting their large-scale applications. The insight into the enzyme mimics using programmable and structurally stable nanomaterial, known as nanozyme, offers an efficient scheme to circumvent the obstacles of natural enzymes, yet, render the biocatalytic functions. In the various categories of nanozymes, porous organic frameworks (POFs) including metal organic frameworks (MOFs), covalent organic frameworks (COFs) and hydrogen-bonded organic frameworks (HOFs) arise enormous attention due to their unique features of ultrahigh surface area, high porosity, and intercommunicating channels. Most importantly, POFs have unambiguous yet predictable topologies, which are structurally favorable for mimicking the active sites as well as microenvironments of natural enzymes. In this review, we overview the advances of POFs nanozymes in which different oxidoreductase- and hydrolase-mimicking activities are involved, with special emphasis on harnessing these diverse activities for conceiving next-generation biosensor targeting micromolecules, metal ions, peptides and proteins, nucleic acids and circulating tumor cells (CTCs), etc. Finally, the current challenges and future perspectives on the design and biosensing applications of POFs nanozymes are discussed. We believe that this review can offer new insight into the access of enzyme mimics with user-defined bioactivity and high stability, and may inspire more interesting biosensing applications.