Mesoporous Metal–Organic Frameworks as Effective Nucleating Agents in Protein Crystallography

Leite, José P.; Rodrigues, Diogo; Ferreira, Susana; Figueira, Flávio; Paz, Filipe A. Almeida; Gales, Luı́s

doi:10.1021/acs.cgd.8b01444

Cited by 14 publications

(7 citation statements)

References 30 publications

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“…Tb-MOF was synthesized as described in (Leite et al 2019) which was adapted with minor modifications from (Park et al 2007). Briefly, terbium nitrate (1.38 × 10 −4 mol) and 4,4′,4″-s-triazine-2,4,6-triyl-tribenzoic acid (4.54 × 10 −4 mol) were dissolved a mixture of dimethylacetamide/methanol/water (4.0/0.8/0.2 mL, respectively).…”

Section: Methodsmentioning

confidence: 99%

Early diagnosis of transthyretin amyloidosis by detection of monomers in plasma microsamples using a protein crystal-based assay

Costa-Rodrigues,

Leite,

Saraiva

et al. 2024

Preprint

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Amyloid diseases are frequently associated with the appearance of an aberrant form of a protein, whose detection enables early diagnosis. In the case of transthyretin amyloidosis, the aberrant protein, the monomers, constitute the smallest species of the amyloid cascade, which creates engineering opportunities for sensing that remain virtually unexplored. Here, a two-step assay is devised, combining molecular sieving and immunodetection, for quantification of circulating monomeric transthyretin in the plasma. It is shown that mesoporous crystals built from biomolecules can selectively uptake transthyretin monomers up to measurable quantities. Furthermore, it was found that the use of endogenous molecules to produce the host framework drastically reduces unspecific adsorption of plasma proteins at the crystal surface, a feature that was observed with metal-organic frameworks. The assay was used to analyse plasma microsamples of patients and healthy controls. It shows a significant increase in the levels of monomeric transthyretin in the patients, proving its usefulness to establish the monomers as soluble and non-invasive marker of the disease. In addition, the assay can evaluate transthyretin stabilizers, an emergent strategy that broadened the treatment approach to the disease. Sensing the initial event of the transthyretin amyloid cascade with the proposed assay can make the difference for early diagnosis and eliminate the currently adopted invasive biopsies modalities for detection of the final products of the aggregation pathway.

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Section: Methodsmentioning

confidence: 99%

Early diagnosis of transthyretin amyloidosis by detection of monomers in plasma microsamples using a protein crystal-based assay

Costa-Rodrigues,

Leite,

Saraiva

et al. 2024

Preprint

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“…Interestingly there was no clear interface between the MOF and lysozyme crystal. Similarly, whilst albumin was not encapsulated, albumin crystals grew on the MOF surface [ 22 ].…”

Section: Large Biomoleculesmentioning

confidence: 99%

“…MOFs can encapsulate various guest molecules, ranging from small cations [ 14 ], to large organic molecules, e.g., drugs [ 15 ], dyes [ 16 ], pharmaceutical and personal care products [ 17 , 18 , 19 ], etc., which makes them suitable to address contemporary challenges in the biomedical, environmental, and industrial field. In particular for applications that involve the encapsulation of biomolecules, or other bulky guest molecules, e.g., enzyme immobilisation [ 20 , 21 ], protein crystallisation [ 22 ], and gene targeting [ 23 ], the isolation of highly porous MOFs (HPMOFs) is essential. The latter refers to MOFs with large pores, and, in this review, these are specified to MOFs that possess surface area higher than 4000 m 2 g −1 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biomedical Applications of Highly Porous Metal–Organic Frameworks

Ahmed

McHugh

Papatriantafyllopoulou

2022

Molecules

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In this review, aspects of the synthesis, framework topologies, and biomedical applications of highly porous metal–organic frameworks are discussed. The term “highly porous metal–organic frameworks” (HPMOFs) is used to denote MOFs with a surface area larger than 4000 m2 g−1. Such compounds are suitable for the encapsulation of a variety of large guest molecules, ranging from organic dyes to drugs and proteins, and hence they can address major contemporary challenges in the environmental and biomedical field. Numerous synthetic approaches towards HPMOFs have been developed and discussed herein. Attempts are made to categorise the most successful synthetic strategies; however, these are often not independent from each other, and a combination of different parameters is required to be thoroughly considered for the synthesis of stable HPMOFs. The majority of the HPMOFs in this review are of special interest not only because of their high porosity and fascinating structures, but also due to their capability to encapsulate and deliver drugs, proteins, enzymes, genes, or cells; hence, they are excellent candidates in biomedical applications that involve drug delivery, enzyme immobilisation, gene targeting, etc. The encapsulation strategies are described, and the MOFs are categorised according to the type of biomolecule they are able to encapsulate. The research field of HPMOFs has witnessed tremendous development recently. Their intriguing features and potential applications attract researchers’ interest and promise an auspicious future for this class of highly porous materials.

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“…To this end, porous nanostructures such as Metal-Organic Frameworks (MOFs), because of their porosity and high surface areas, are highly regarded for biological applications [ 19 , 20 ]. Recent research on MOFs, focused on the ability to control the crystallite size down to the nanometre range (NMOFs), has been opening the door to many unique properties that their micrometre counterparts do not have [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Porphyrin NanoMetal-Organic Frameworks as Cancer Theranostic Agents

2022

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Metal-Organic Frameworks (MOFs) are hybrid multifunctional platforms that have found remarkable applications in cancer treatment and diagnostics. Independently, these materials can be employed in cancer treatment as intelligent drug carriers in chemotherapy, photothermal therapy, and photodynamic therapy; conversely, MOFs can further be used as diagnostic tools in fluorescence imaging, magnetic resonance imaging, computed tomography imaging, and photoacoustic imaging. One essential property of these materials is their great ability to fine-tune their composition toward a specific application by way of a judicious choice of the starting building materials (metal nodes and organic ligands). Moreover, many advancements were made concerning the preparation of these materials, including the ability to downsize the crystallites yielding nanoporous porphyrin MOFs (NMOFs) which are of great interest for clinical treatment and diagnostic theranostic tools. The usage of porphyrins as ligands allows a high degree of multifunctionality. Historically these molecules are well known for their reactive oxygen species formation and strong fluorescence characteristics, and both have proved helpful in cancer treatment and diagnostic tools. The anticipation that porphyrins in MOFs could prompt the resulting materials to multifunctional theranostic platforms is a reality nowadays with a series of remarkable and ground-breaking reports available in the literature. This is particularly remarkable in the last five years, when the scientific community witnessed rapid development in porphyrin MOFs theranostic agents through the development of imaging technologies and treatment strategies for cancer. This manuscript reviews the most relevant recent results and achievements in this particular area of interest in MOF chemistry and application.

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Mesoporous Metal–Organic Frameworks as Effective Nucleating Agents in Protein Crystallography

Cited by 14 publications

References 30 publications

Early diagnosis of transthyretin amyloidosis by detection of monomers in plasma microsamples using a protein crystal-based assay

Early diagnosis of transthyretin amyloidosis by detection of monomers in plasma microsamples using a protein crystal-based assay

Synthesis and Biomedical Applications of Highly Porous Metal–Organic Frameworks

Porphyrin NanoMetal-Organic Frameworks as Cancer Theranostic Agents

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