Liposome-coated iron fumarate metal-organic framework nanoparticles for combination therapy

One of the main problems for effective treatment of cancer is resistances, which often require combination therapy-for effective treatment. While there are already some potential drug carriers-e.g., liposomes, available for treatment-the effective loading and retention of the desired drug ratio can be challenging. To address this challenge, we propose a new type of drug carrier: liposome-coated metal-organic framework (MOF) nanoparticles. They combine the advantages of liposomes with an easy and efficient loading process. In this work, we present the successful synthesis of liposome-coated MOF nanoparticles via the fusion method. The resulting particles, once loaded, show no premature leakage and an efficient release. Their successful loading with both single and multiple drugs at the same time makes them an interesting candidate for use in combination therapy

The Chemistry of Reticular Framework Nanoparticles: MOF, ZIF, and COF Materials

Nanoparticles have become a vital part of a vast number of established processes and products;they are used as catalysts, in cosmetics, and even by the pharmaceutical industry. Despite this, however, the reliable and reproducible production of functional nanoparticles for specific applications remains a great challenge. In this respect, reticular chemistry provides methods for connecting molecular building blocks to nanoparticles whose chemical composition, structure, porosity, and functionality can be controlled and tuned with atomic precision. Thus, reticular chemistry allows for the translation of the green chemistry principle of atom economy to functional nanomaterials, giving rise to the multifunctional efficiency concept. This principle encourages the design of highly active nanomaterials by maximizing the number of integrated functional units while minimizing the number of inactive components. State-of-the-art research on reticular nanoparticles-metal-organic frameworks, zeolitic imidazolate frameworks, and covalent organic frameworks-is critically assessed and the beneficial features and particular challenges that set reticular chemistry apart from other nanoparticle material classes are highlighted. Reviewing the power of reticular chemistry, it is suggested that the unique possibility to efficiently and straightforwardly synthesize multifunctional nanoparticles should guide the synthesis of customized nanoparticles in the future

Exploiting Locality of Churn for FIB Aggregation

Snapshots of the Forwarding Information Base (FIB) in Internet routers can be compressed (or aggregated) to at least half of their original size, as shown by previous studies. In practice however, the permanent stream of updates to the FIB due to routing updates complicates FIB aggregation: keeping an optimally aggregated FIB in face of these routing updates is algorithmically challenging. A sensible trade-off has to be found between the aggregation gain and the number of changes to the aggregated FIB. This paper is the first to investigate whether the spatial and temporal locality properties of updates to the tree-like FIB data structure can be leveraged by online FIB aggregation. Our contributions include (a) an empirical study of the locality of updates in public Internet routing data, (b) the specification and simulations of our Locality-aware FIB Aggregation algorithm (LFA), and (c) a competitive analysis that sheds light on the performance of online algorithms under worst-case update streams. Our results show that even a simple algorithm like LFA can effectively exploit the locality of FIB churn to keep low the number of updates to the aggregated FIB, as most FIB updates affect only a small number of regions in the FIB

Novel sol-gel prepared zinc fluoride: synthesis, characterisation and acid-base sites analysis

The fluorolytic sol-gel route sets a milestone in the development of synthesis methods for nanoscopic fluoride materials. They exhibit fundamentally distinct properties in comparison to classically prepared metal fluorides. To broaden this area, we report in this paper the first fluorolytic sol-gel synthesis of ZnF₂. The obtained sol was studied with dynamic light scattering (DLS). The dried ZnF₂ xerogel was investigated with elemental analysis, thermal analysis, powder X-ray diffraction (XRD), solid-state MAS NMR, and N₂ adsorption-desorption measurements. The characterisations revealed a remarkably high surface area of the sol-gel prepared ZnF₂. To determine key parameters deciding its prospects in future catalytic applications, we studied the surface acidity-basicity by using in situ FTIR with different probe molecules. Compared to the previously established MgF₂, weaker Lewis acid sites are predominant on the surface of ZnF2 with some base sites, indicating its potential as a heterogeneous catalyst component. In short, we believe that the successful synthesis and detailed characterisation of nanoscopic ZnF₂ allow follow-up work exploring its applications, and will lead to studies of more metal fluorides with similar methods

Clinically Approved MRI Contrast Agents as Imaging Labels for a Porous Iron‐Based MOF Nanocarrier: A Systematic Investigation in a Clinical MRI Setting

Metal‐organic framework nanoparticles (MOF NPs) are a promising class of NP systems that offer versatile and tunable properties. Creating a magnetic resonance imaging (MRI)‐MOF NP platform as a basis for a theranostic drug delivery system is considered an auspicious approach, as MRI is a routinely used clinical method allowing real‐time imaging. So far clinically approved MRI contrast agents (CAs) have not been investigated systematically for the visualization of loading and release from MOF NPs. Here, loading and release of six clinically approved CAs from the MOF MIL‐100(Fe) are investigated in a clinical MRI setting. Standard procedures, beginning with sample preparation up to MRI methods, are established for that purpose. Results are reproduced and verified by Inductively Coupled Plasma Atomic Emission Spectrometry (ICP‐AES) and thiocyanate testing. The macrocyclic CA gadoterate meglumine is identified as the best CA candidate for labeling MIL‐100(Fe). The CA is successfully loaded after 1 h, and also effectively released within the first hour. The MR‐active CA and iron residuals in supernatants are differentiable based on MRI only and concentrations can be successfully calculated. The presented systematic approach suggests procedures and MRI‐methodology that can be used as blueprint strategy when labeling porous NPs with clinically approved MRI CAs

Beyond Frameworks: Structuring Reticular Materials across Nano‐, Meso‐, and Bulk Regimes

Reticular materials are of high interest for diverse applications, ranging from catalysis and separation to gas storage and drug delivery. These open, extended frameworks can be tailored to the intended application through crystal‐structure design. Implementing these materials in application settings, however, requires structuring beyond their lattices, to interface the functionality at the molecular level effectively with the macroscopic world. To overcome this barrier, efforts in expressing structural control across molecular, nano‐, meso‐, and bulk regimes is the essential next step. In this Review, we give an overview of recent advances in using self‐assembly as well as externally controlled tools to manufacture reticular materials over all the length scales. We predict that major research advances in deploying these two approaches will facilitate the use of reticular materials in addressing major needs of society

Vorhersage der MOF‐Synthese durch automatisches Data‐Mining und maschinelles Lernen

Trotz großer Fortschritte auf dem Gebiet der metallorganischen Gerüststrukturen (MOF) ist das volle Potential des Maschinellen Lernens (ML) für die Vorhersage von MOF-Syntheseparametern bisher noch nicht erschlossen. In diesem Beitrag wird dargestellt, wie Methoden des ML für die Rationalisierung und Beschleunigung von MOF-Entwicklungsverfahren eingesetzt werden können, indem die Synthesebedingungen der MOFs direkt anhand ihrer Kristallstruktur vorhergesagt werden. Unser Ansatz stützt sich auf: i) die Erstellung der ersten MOF-Synthese-Datenbank durch automatische Extraktion der Syntheseparameter aus der Fachliteratur, ii) das Trainieren und die Optimierung von ML-Modellen mit Daten der MOF-Datenbank und iii) die ML basierte Vorhersage der Synthesebedingungen neuer MOF-Strukturen. Schon jetzt übertreffen die Ergebnisse der Vorhersagemodelle die Vorhersagen menschlicher ExpertInnen, welche in einer Befragung ermittelt wurden. Die automatisierte Synthesevorhersage ist über ein Web-Tool unter https://mof-synthesis.aimat.science verfügbar

MOF Synthesis Prediction Enabled by Automatic Data Mining and Machine Learning**

Despite rapid progress in the field of metal–organic frameworks (MOFs), the potential of using machine learning (ML) methods to predict MOF synthesis parameters is still untapped. Here, we show how ML can be used for rationalization and acceleration of the MOF discovery process by directly predicting the synthesis conditions of a MOF based on its crystal structure. Our approach is based on: i) establishing the first MOF synthesis database via automatic extraction of synthesis parameters from the literature, ii) training and optimizing ML models by employing the MOF database, and iii) predicting the synthesis conditions for new MOF structures. The ML models, even at an initial stage, exhibit a good prediction performance, outperforming human expert predictions, obtained through a synthesis survey. The automated synthesis prediction is available via a web‐tool on https://mof‐synthesis.aimat.science

Metal–Organic Framework Nanoparticles Induce Pyroptosis in Cells Controlled by the Extracellular pH

Ion homeostasis is essential for cellular survival, and elevated concentrations of specific ions are used to start distinct forms of programmed cell death. However, investigating the influence of certain ions on cells in a controlled way has been hampered due to the tight regulation of ion import by cells. Here, it is shown that lipid‐coated iron‐based metal–organic framework nanoparticles are able to deliver and release high amounts of iron ions into cells. While high concentrations of iron often trigger ferroptosis, here, the released iron induces pyroptosis, a form of cell death involving the immune system. The iron release occurs only in slightly acidic extracellular environments restricting cell death to cells in acidic microenvironments and allowing for external control. The release mechanism is based on endocytosis facilitated by the lipid‐coating followed by degradation of the nanoparticle in the lysosome via cysteine‐mediated reduction, which is enhanced in slightly acidic extracellular environment. Thus, a new functionality of hybrid nanoparticles is demonstrated, which uses their nanoarchitecture to facilitate controlled ion delivery into cells. Based on the selectivity for acidic microenvironments, the described nanoparticles may also be used for immunotherapy: the nanoparticles may directly affect the primary tumor and the induced pyroptosis activates the immune system

Highly oriented surface-growth and covalent dye labeling of mesoporous metal-organic frameworks

Mesoporous amino-functionalized metal-organic framework thin films with the UiO-68 topology were grown in a highly oriented fashion on two different self-assembled monolayers on gold. The oriented MOF films were covalently modified with the fluorescent dye Rhodamine B inside the pore system, as demonstrated with size-selective fluorescence quenching studies. Our study suggests that mesoporous metal-organic frameworks are promising hosts for the covalent attachment of numerous functional moieties in a molecularly designed crystalline environment. © The Royal Society of Chemistry 2012