Embedding Functional Biomacromolecules within Peptide‐Directed Metal–Organic Framework (MOF) Nanoarchitectures Enables Activity Enhancement

Abstract

Rationally tailoring ar obust artificial coating can enhance the lifetime of fragile biomacromolecules.H owever, the coating also can restrain the activity of the guest because of the decreased substrate accessibility.H erein, we report ap eptide-directed strategy that enables in situ tailoring of the MOFshrouded biohybrids into controllable nanoarchitectures.T he MOF biohybrid can be shaped from different 3D microporous architectures into a2 Dm esoporous layer by ap eptide modulator.U sing this mild strategy,w es how that the nanoarchitectures of the MOF coatings significantly affect the biological functions of the contained biomacromolecules.The biomacromolecules entrapped within the novel 2D mesoporous spindle-shaped MOFs (2D MSMOFs) have significantly increased bioactivity compared to when encased within the hitherto explored 3D microporous MOFs.T he improvement results from the shortened diffusion path and enlarged pore channel in 2D MSMOFs.M eanwhile,t he thin 2D MSMOF layer also can providee xcellent protection of the hosted biomacromolecules or protein-scaffolded biominerals through structural confinement.

Protein-directed, hydrogen-bonded biohybrid framework

“…The diversity of this approach was due to the common presence of amino acid residues in proteins, which helps mediate the assembly through hydrogen-bond interaction. Accordingly, the calculated protein content in this protein-directed assembly ranged from 24.3% to 47.9% (Figure 2I; Table S2), which is much higher that the values reported in proteins@MOFs (usually less than 15%), [24][25][26][27][28][29][30][31][32][33][34][35] and also outclass the reported values where the proteins are simply precipitated into the growing HOFs (6.0% G 0.5%). 38…”

“…These values were well accorded with the reported enzyme contents in ZIF hybrids using biomimetic mineralization approach. [24][25][26][27][28][29][30][31][32][33][34][35] As a comparison, 32.7% and 52.3% Cyt c contents were observed in Cyt c@HBF-1 and Cyt c@HBF-2, respectively, showing an order of magnitude higher than those in Cyt c@ZIFs. Such enhancement on enzymes' incorporation in HBFs was also validated by using other enzyme (HRP) as the building blocks (Figure 5B, detailed characterizations seen in Figures S49-S51), attributing to the enzyme-directed assembly.…”

“…28 Zeolitic imidazolate frameworks (ZIFs, such as ZIF-8, and ZIF-90) are the hitherto used MOF matrices for such protein biohybrids because of their biocompatible synthesis conditions that shield proteins against denaturation during the assembly. [24][25][26][27][28][29][30][31][32] Unfortunately, the structure topologies observed for the proteins@ZIF hybrids possess narrow crystallographic pore apertures (typically ~3.4 A ˚) that significantly limit the diffusion of substrate and accessibility of inner proteins for biocatalytic transformations. [33][34][35] Meanwhile, ZIFs are extremely susceptible at mildly acidic pH, 36 but the optimal activities for many proteins are at acidic conditions.…”

“…[33][34][35] Meanwhile, ZIFs are extremely susceptible at mildly acidic pH, 36 but the optimal activities for many proteins are at acidic conditions. 37 In addition, from the view of the assembly principle, the MOF host is still the main ingredient of the biohybrid and the contents of protein is low (usual < 15% w/w), [24][25][26][27][28][29][30][31][32][33][34][35] and the successful assembly relies on the surface charge and chemistry of the given protein. 24,31 Very recently, a breakthrough by Doonan and co-workers showed the possibility of packaging proteins into another crystalline framework: hydrogen-bonded organic framework (HOF).…”

Metal–organic frameworks (MOFs) as host materials for the enhanced delivery of biomacromolecular therapeutics

“…In-situ encapsulation is an alternative strategy to pore encapsulation, which can accommodate a broader spectrum of biomacromolecules irrespective of the size of biomacromolecules. 33,34 The principle of this strategy is that the MOF precursor undergoes a self-assembly process surrounding the biological macromolecules, and then the biomolecules are uniformly encapsulated inside the MOF material to obtain a hostguest supramolecular-ensemble. However, only a limited number of MOFs based materials have been used for in-situ encapsulation of biomacromolecules (e.g., ZIF-8 and ZIF-90).…”