Self‐Assembly of Oriented Antibody‐Decorated Metal–Organic Framework Nanocrystals for Active‐Targeting Applications

Alt, Karen; Carraro, Francesco; Jap, Edwina; Linares‐Moreau, Mercedes; Riccò, Raffaele; Righetto, Marcello; Bogar, Marco; Amenitsch, Heinz; Hashad, Rania A.; Doonan, Christian J.; Hagemeyer, Christoph E.; Falcaro, Paolo

doi:10.1002/adma.202106607

Cited by 30 publications

(23 citation statements)

References 41 publications

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“…We also checked if the phase was Zn 2 (mIM) 2 (CO 3 ). The FT-IR pattern of Ad5@aZn-mIM and aZn-mIM showed no asymmetric stretching modes of carbonate around 1583 and 1369 cm –1 and no bending mode of carbonate around 827 cm –1 (Figure G and Figure S14). Next, X-ray photon spectroscopy (XPS) was employed to examine the chemical interactions between Zn 2+ and the ligands of Ad5@His-aZn-mIM.…”

Section: Resultsmentioning

confidence: 99%

Conformation-Stabilized Amorphous Nanocoating for Rational Design of Long-Term Thermostable Viral Vaccines

Zhang

Hao

Lin

et al. 2022

ACS Appl. Mater. Interfaces

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Despite the great potency of vaccines to combat infectious diseases, their global use is hindered by a lack of thermostability, which leads to a constant need for cold-chain storage. Here, aiming at long-term thermostability and eliminating cold-chain requirements of bioactive vaccines, we propose that efforts should focus on tailoring the conformational stability of vaccines. Accordingly, we design a nanocoating composed of histidine (His)-coordinated amorphous Zn and 2-methylimidazolate complex (His-aZn-mIM) on single nanoparticles of viral vaccines to introduce intramolecular coordinated linkage between viruses and the nanocoatings. The coordinated nanocoating enhances the rigidity of proteins and preserves the vaccine's activity. Importantly, integrating His into the original Zn−N coordinative environment symbiotically reinforces its tolerance to biological and hydrothermal solutions, resulting in the augmented thermostability following the Hofmeister effect. Thus, even after storage of His-aZn-mIM encapsulated Human adenovirus type 5 (Ad5@His-aZn-mIM) at 25 °C for 90 d, the potency loss of the coated Ad5 is less than 10%, while the native Ad5 becomes 100% ineffective within one month. Such a nanocoating gains thermostability by forming an ultrastable hydration shell, which prevents viral proteins from unfolding under the attack of hydration ions, providing a conformational stabilizer upon heat exposure. Our findings represent an easy-access biomimetic platform to address the long-term vaccine storage without the requirement of a cold chain.

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Section: Resultsmentioning

confidence: 99%

Conformation-Stabilized Amorphous Nanocoating for Rational Design of Long-Term Thermostable Viral Vaccines

Zhang

Hao

Lin

et al. 2022

ACS Appl. Mater. Interfaces

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“…Intense catalytic activity and carbon nanoflower hierarchical structure makes FeCo@CNT as co-reaction accelerators, generating more TPA •+ radicals to react with more Eu-MOFs to achieve the ECL emission amplification. In the meantime, heptapeptide HWRGWVC (HWR), which controlled the orientation of the antibody (Ab), ensured the orderly immobilization of the fragment-crystallizable (Fc) region on the nanocarrier. , FeCo@CNT with HWR constructed a high cultivation efficiency matrix biosensing interface via an amide, allowing the fragment antigen-binding (Fab) regions free to target specific antigens to conjugate . With carbohydrate antigen 242 (CA 242) as the analytical model, the as-fabricated biosensor achieves excellent ECL performance.…”

Section: Introductionmentioning

confidence: 99%

Mixed-Ligand-Regulated Self-Enhanced Luminous Eu-MOF as an ECL Signal Probe for an Oriented Antibody-Decorated Biosensing Platform

Dong

Liu

et al. 2022

Anal. Chem.

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The self-luminescence behavior of lanthanide MOFs (Ln-MOFs) due to the unique antenna effect is considered to be a promising electrochemiluminescence (ECL) emission for biosensors. It is more challenging for Ln-MOFs on account of the difficulty to stimulate Ln ions with the desired energy-transfer efficiency to produce stronger ECL emissions at a low potential. Here, guided by a second ligand-assisted energy-transfer strategy, we present an efficient self-enhanced luminescence mixed-ligand Eu-MOF as an ECL signal probe for an oriented antibody-decorated biosensing platform with a low detection limit and a broad detection range. Diamino terephthalic acid (NH2–H2BDC) and 1,10-phenanthroline (Phen) were selected as the first and second ligands, respectively, to form highly conjugated structures, as well as suppress the nonradiative energy transfer. Impressively, Phen precisely adjusts the energy gap between the triplet ligand and the excited state of Eu3+, realizing the self-enhancement of ECL efficiency of the Eu-MOF. The mixed ligand adjusted the molar ratio to obtain the stable and strong ECL signal at a lowered triggering potential (0.83 V). In addition, FeCo@CNT features densely active FeCo sites along with a rich hierarchy conductive carbon nanotube (CNT) network, which is efficiently a co-reaction accelerator to produce more TPA•+ radicals to accelerate the reduction process of the Eu-MOF for achieving the ECL emission amplification. FeCo@CNT with heptapeptide HWRGWVC (HWR) constructed a matrix biosensing interface that allowed the fragment antigen-binding (Fab) regions to target specific antigens and enhance the incubation efficiency. The present study has gone some way toward designing a self-enhanced luminous Eu-MOF, thus giving new fresh impetus to develop high-performance ECL emitters for biological analysis.

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“…Examples of established and emerging MAbs for cancer therapy are compared in the Supporting Information in Supporting Note 1, Table S1. The global therapeutic MAbs market reached approximately 204 billion USD in 2022 from a base of 0.3 billion USD in 1997, 115 billion USD in 2018, is projected to exceed 300 billion USD by 2025, and is expected to hit 425 billion USD by 2028. − Deployment of MAbs is not limited to cancer, but also treatment of asthma, autoimmune diseases, septicemia, viral infections, chronic inflammatory, and cardiovascular diseases. , MAbs are recommended for treatment of COVID-19 in ambulatory patients with a high risk of clinical progression by both the National Institutes of Health and the Infectious Diseases Society of America. , MAbs can be conjugated with functional nanomaterials such as quantum dots (QDs), gold, and iron oxide nanoparticles for sensing and imaging as well as smart drug delivery applications. , …”

Section: Introductionmentioning

confidence: 99%

“…4−6 Deployment of MAbs is not limited to cancer, but also treatment of asthma, 7 autoimmune diseases, 8 septicemia, 9 viral infections, 10 chronic inflammatory, 11 and cardiovascular diseases. 12,13 MAbs are recommended for treatment of COVID-19 in ambulatory patients with a high risk of clinical progression by both the National Institutes of Health and the Infectious Diseases Society of America. 14,15 MAbs can be conjugated with functional nanomaterials such as quantum dots (QDs), 16 gold, 17 and iron oxide nanoparticles 18 for sensing and imaging as well as smart drug delivery applications.…”

Section: Introductionmentioning

confidence: 99%

Copolyelectrolyte-Based Nanocapsules for Oral Monoclonal Antibody Therapy: A Mesoscale Modeling Survey

Nikkhah

Thompson

2022

Biomacromolecules

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Antibody therapy generally requires parenteral injection to attain the required bioavailability and pharmacokinetics, but improved formulations may slow enzymatic degradation of the antibody in the gastrointestinal tract, permitting the use of noninvasive oral delivery. Rationally designed carrier materials can potentially improve therapeutic activity both by shielding fragile biopharmaceuticals from proteolytic degradation and targeting specific receptors in vivo. One potentially useful class of protein carriers is block copolyelectrolytes, one polyelectrolyte plus one neutral hydrophilic polymer block, that self-assemble into stable micelles, providing a simple and biocompatible nanocapsule separating the protein from the outer medium. Here, we develop and implement an integrated mesoscale model to design molecular structures for block copolyelectrolyte nanocapsules predicted to protect Trastuzumab, an antibody used to treat breast cancer, in the low pH gastrointestinal tract and to selectively release this antibody in the more neutral intestinal environment. The simulations show a tightly packed self-assembled core–shell structure at pH = 3 that is ruptured and dynamically reassembled into a weaker structure at pH = 7. Our model identifies that the designed block copolyelectrolyte characteristics, such as block length ratio, can control the level of drug protection and release in vivo, providing simple design rules for engineering polyelectrolyte-based formulations that may allow oral administration of targeted antibody chemotherapies.

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Self‐Assembly of Oriented Antibody‐Decorated Metal–Organic Framework Nanocrystals for Active‐Targeting Applications

Abstract: to be extended from antibody-based sensing to diagnostic and therapeutic applications.

Cited by 30 publications

References 41 publications

Conformation-Stabilized Amorphous Nanocoating for Rational Design of Long-Term Thermostable Viral Vaccines

Conformation-Stabilized Amorphous Nanocoating for Rational Design of Long-Term Thermostable Viral Vaccines

Mixed-Ligand-Regulated Self-Enhanced Luminous Eu-MOF as an ECL Signal Probe for an Oriented Antibody-Decorated Biosensing Platform

Copolyelectrolyte-Based Nanocapsules for Oral Monoclonal Antibody Therapy: A Mesoscale Modeling Survey

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