Antibodies@MOFs: An In Vitro Protective Coating for Preparation and Storage of Biopharmaceuticals

Abstract

Antibodies have emerged as a fast‐growing category of biopharmaceuticals that have been widely applied in scientific research, medical diagnosis, and disease treatment. However, many antibodies and other biopharmaceuticals display inferior biophysical properties, such as low stability and a propensity to undergo aggregation. Enhancing the stability of biopharmaceuticals is essential for their wide applications. Here, a facile in vitro protective coating strategy based on metal–organic frameworks (MOFs) is proposed to efficiently protect antibodies against perturbation environments and quickly recover them from the MOFs before usage, which avoids introducing protective additives into the body, which may cause biosafety risks. The protected antibodies exhibit extraordinary thermal, chemical, and mechanical stabilities, and they can survive for long‐term storage (>3 weeks) under severe temperature variation (4 ↔ 50 °C) at a fast ramp rate (25 °C min−1). More importantly, the encapsulated antibodies can be easily released as quickly as 10 s with high efficiency (≈100%) to completely remove the MOFs before use. This study paves a new avenue for the facile preparation and storage of biopharmaceuticals represented by antibodies under ambient or perturbation conditions, which may greatly broaden and promote the applications of both MOFs and biopharmaceuticals.

Peroxidase Encapsulated in Peroxidase Mimics via in situ Assembly with Enhanced Catalytic Performance

“…The resultant enzyme hybrid nanoflower exhibited remarkably enhanced thermal stability. The versatility of this process has driven the construction of bioactive molecules with protective inorganic shells including enzymes, antibodies, vaccine and cells . Moreover, nanostructured shells were not limited to metal phosphate crystals and metal organic frameworks (MOFs) .…”

Modulating the Biofunctionality of Metal–Organic‐Framework‐Encapsulated Enzymes through Controllable Embedding Patterns

“…When the enzyme was exposed to harsh conditions (e.g., in the presence of chemical solvent or at high temperature), the robust ZIF-8 exoskeleton could provide an "armour-like" protecting effect against the denaturation of the enzymes. [15,[19][20][21] Under conditions that would normally denature the enzymes,H RP-A@ZIF-8 thus displayed higher catalytic activity than the free HRP. (Figure 5E and F).…”

“…[10][11][12][13][14][15] In this approach, biomacromolecules of different size and even viruses and cells were encased within MOFs that possessed significantly smaller pore dimensions than themselves. [15][16][17][18][19] It was demonstrated that the porous MOF exoskeletons could not only improve the stability of the encapsulated enzymes through structural confinement, but also allow selective transport of the guest via the accessible micropores network of the exoskeleton. [20,21] Such symbiotic reinforcement effects between MOFs and enzymes endowed MOF-embedded enzymes with great potential in sophisticated applications,i ncluding biosensing, [22] biocatalysis, [21] and enzymatic carrier for cancer therapy.…”

“…[23][24][25] However,t hese initial studies mainly focused on embedding functional enzymes in protective MOF cages without emphasizing the embedding patterns,a nd only limited consideration has been given to the conversion of the enzymatic biofunctionality after entrapment by aMOFs.This is worthy of attention, as the de novo encapsulating process could result in inactivation of enzymes due to their fragile nature.Indeed, we noticed that in some cases the enzymes are partially or even completely inactive when encapsulated within zeolitic imidazolate framework-8 (ZIF-8) crystals (see below), aw idely used exoskeleton for in situ enzyme encapsulation. [10,11,[14][15][16][17][18][19][20][21][22][23][24][25][26] In this work, we sought to reveal how embedding patterns influence the biofunctionality of enzymes encapsulated within ZIF-8 and to develop an ew strategy to produce enzymes@ZIF-8 biocomposites that maintain high enzymatic activity.W ec hose six typical enzymes as models, glucose oxidase (GOx), cytochrome C( Cyt C), horseradish peroxidase (HRP), catalase (CAT), urate oxidase (UOx) and alcohol dehydrogenase (ADH). These enzymes are extremely valuable across aw ide range of industries,i ncluding biofuel, food, and biosensing, and as therapeutics in the pharmaceutical industry.O ur findings show that ZIF-8-embedded enzymes (enzymes@ZIF-8), wherein the enzymes were encapsulated through rapid self-triggered nucleation around their surface,maintain high enzymatic activity,comparable to the free enzymes.I nt he other encapsulation process,w here the MOF nucleated as they normally would in the absence of the enzymes,a nd the enzymes were encapsulated through slow coprecipitation, the obtained enzymes@ZIF-8 tended to be inactive due to unfolding effects and competing coordination caused by the 2-methyl imidazole (HmIM) ligand.…”

Nanobiohybrids: Materials approaches for bioaugmentation

“…However, most antibodies display poor stability and a tendency to undergo aggregation, which significantly limits their practical applications. To address this challenge, extra protective coatings were applied to preserve the biorecognition functionalities of the antibodies (94,95). In Singamaneni and co-workers' report, ZIF-8 was directly coated on antibody-functionalized gold nanorod biosensors (94).…”