Biomedical metal–organic framework materials : perspectives and challenges

The authors gratefully acknowledge financial support from the German Research Foundation (DFG: LA2937/4-1; SH1223/1-1; SFB 1066; GRK/RTG 2735 (project number 331065168)), the German Federal Ministry of Research and Education (BMBF: Gezielter Wirkstofftransport, PP-TNBC, Project No. 16GW0319K) and the European Research Council (ERC: Meta-Targeting (864121)). The financial support from Welch Foundation (AT-1989-20220331) and from the Human Frontier Science Program (HFSP, within the project RGP0047/2022) are also acknowledged. The authors thank the European Union (European Cooperation in Science and Technology) for the COST Action EU4MOFs (CA22147). Figures were created using BioRender.com.Metal–organic framework (MOF) materials are gaining significant interest in biomedical research, owing to their high porosity, crystallinity, and structural and compositional diversity. Their versatile hybrid organic/inorganic chemistry endows MOFs with the capacity to retain organic (drug) molecules, metals, and gases, to effectively channel electrons and photons, to survive harsh physiological conditions such as low pH, and even to protect sensitive biomolecules. Extensive preclinical research has been carried out with MOFs to treat several pathologies and, recently, their integration with other biomedical materials such as stents and implants has demonstrated promising performance in regenerative medicine. However, there remains a significant gap between MOF preclinical research and translation into clinically and societally relevant medicinal products. Here, the intrinsic features of MOFs are outlined and their suitability to specific biomedical applications such as detoxification, drug and gas delivery, or as (combination) therapy platforms is discussed. Furthermore, relevant examples of how MOFs have been engineered and evaluated in different medical indications, including cancer, microbial, and inflammatory diseases is described. Finally, the challenges facing their translation into the clinic are critically examined, with the goal of establishing promising research directions and more realistic approaches that can bridge the translational gap of MOFs and MOF‐containing (nano)materials.Publisher PDFPeer reviewe

Biomedical metal–organic framework materials:perspectives and challenges

Metal–organic framework (MOF) materials are gaining significant interest in biomedical research, owing to their high porosity, crystallinity, and structural and compositional diversity. Their versatile hybrid organic/inorganic chemistry endows MOFs with the capacity to retain organic (drug) molecules, metals, and gases, to effectively channel electrons and photons, to survive harsh physiological conditions such as low pH, and even to protect sensitive biomolecules. Extensive preclinical research has been carried out with MOFs to treat several pathologies and, recently, their integration with other biomedical materials such as stents and implants has demonstrated promising performance in regenerative medicine. However, there remains a significant gap between MOF preclinical research and translation into clinically and societally relevant medicinal products. Here, the intrinsic features of MOFs are outlined and their suitability to specific biomedical applications such as detoxification, drug and gas delivery, or as (combination) therapy platforms is discussed. Furthermore, relevant examples of how MOFs have been engineered and evaluated in different medical indications, including cancer, microbial, and inflammatory diseases is described. Finally, the challenges facing their translation into the clinic are critically examined, with the goal of establishing promising research directions and more realistic approaches that can bridge the translational gap of MOFs and MOF‐containing (nano)materials

The Importance of Dean Flow in Microfluidic Nanoparticle Synthesis: A ZIF-8 Case Study

The Dean Flow, a physics phenomenon that accounts for the impact of channel curvature on fluid dynamics, has great potential to be used in microfluidic synthesis of nanoparticles. This study explores the impact of the Dean Flow on the synthesis of ZIF-8 particles. Several variables that influence the Dean Equation (the mathematical expression of Dean Flow) are tested to validate the applicability of this expression in microfluidic synthesis, including the flow rate, radius of curvature, channel cross sectional area, and reagent concentration. It is demonstrated that the current standard of reporting, providing only the flow rate and crucially not the radius of curvature, is an incomplete description that will invariably lead to irreproducible syntheses across different laboratories. An alternative standard of reporting is presented and it is demonstrated how the sleek and simple math of the Dean Equation can be used to precisely tune the final dimensions of high quality, monodisperse ZIF-8 nanoparticles between 40 and 700 nm

Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei

In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.Boettcher Foundation's Webb-Waring Biomedical Research Program; Boettcher Collaboration Grant; Research Corporation Cottrell College Science Award; National Institute of Allergy and Infectious Diseases (US):R01AI114685; Ministerio de Economia, Industria y Competitividad (España) SAF2015-71444-P; SAF2015-68042-R; SAF2016-79957-R; Junta de Andalucia CTS-7282; Subdireccion General de Redes y Centros de Investigacion Cooperativa (RICET) RD16/0027/0019, DG-P RD16/0027/0014; NSF-MRI CHE-1429567Peer reviewe

Multi-scale mapping of Australia’s terrestrial and blue carbon stocks and their continental and bioregional drivers

Abstract The soil in terrestrial and coastal blue carbon ecosystems is an important carbon sink. National carbon inventories require accurate assessments of soil carbon in these ecosystems to aid conservation, preservation, and nature-based climate change mitigation strategies. Here we harmonise measurements from Australia’s terrestrial and blue carbon ecosystems and apply multi-scale machine learning to derive spatially explicit estimates of soil carbon stocks and the environmental drivers of variation. We find that climate and vegetation are the primary drivers of variation at the continental scale, while ecosystem type, terrain, clay content, mineralogy and nutrients drive subregional variations. We estimate that in the top 0–30 cm soil layer, terrestrial ecosystems hold 27.6 Gt (19.6–39.0 Gt), and blue carbon ecosystems 0.35 Gt (0.20–0.62 Gt). Tall open eucalypt and mangrove forests have the largest soil carbon content by area, while eucalypt woodlands and hummock grasslands have the largest total carbon stock due to the vast areas they occupy. Our findings suggest these are essential ecosystems for conservation, preservation, emissions avoidance, and climate change mitigation because of the additional co-benefits they provide