Validating Metal?Organic Framework Nanoparticles for Their Nanosafety in Diverse Biomedical Applications

Metal?organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterials to patients, it is imperative to understand their potential health risks. In this study, the nanosafety of different MOF nanoparticles is analyzed comprehensively for diverse medical applications. The authors first evaluate the effects of MOFs on human endothelial and mouse lung cells, which constitute a first line of defense upon systemic blood?mediated and local lung?specific applications of nanoparticles. Second, we validated these MOFs for multifunctional surface coatings of dental implants using human gingiva fibroblasts. Moreover, biocompatibility of MOFs is assessed for surface coating of nerve guidance tubes using human Schwann cells and rat dorsal root ganglion cultures. The main finding of this study is that the nanosafety and principal suitability of our MOF nanoparticles as novel agents for drug delivery and implant coatings strongly varies with the effector cell type. We conclude that it is therefore necessary to carefully evaluate the nanosafety of MOF nanomaterials with respect to their particular medical application and their interacting primary cell types, respectively.</p

Validating Metal?Organic Framework Nanoparticles for Their Nanosafety in Diverse Biomedical Applications

Metal?organic frameworks (MOFs) are promising platforms for the synthesis of nanoparticles for diverse medical applications. Their fundamental design principles allow for significant control of the framework architecture and pore chemistry, enabling directed functionalization for nanomedical applications. However, before applying novel nanomaterials to patients, it is imperative to understand their potential health risks. In this study, the nanosafety of different MOF nanoparticles is analyzed comprehensively for diverse medical applications. The authors first evaluate the effects of MOFs on human endothelial and mouse lung cells, which constitute a first line of defense upon systemic blood?mediated and local lung?specific applications of nanoparticles. Second, we validated these MOFs for multifunctional surface coatings of dental implants using human gingiva fibroblasts. Moreover, biocompatibility of MOFs is assessed for surface coating of nerve guidance tubes using human Schwann cells and rat dorsal root ganglion cultures. The main finding of this study is that the nanosafety and principal suitability of our MOF nanoparticles as novel agents for drug delivery and implant coatings strongly varies with the effector cell type. We conclude that it is therefore necessary to carefully evaluate the nanosafety of MOF nanomaterials with respect to their particular medical application and their interacting primary cell types, respectively.</p

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.</p

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.</p

Mass Measurements Reveal Preferential Sorption of Mixed Solvent Components in Porous Nanoparticles

The interplay of physical and chemical properties at the nanometer scale provides porous nanoparticles with unique sorption and interaction capabilities. These properties have aroused great interest toward this class of materials for application ranging from chemical and biological sensing to separation and drug delivery. However, so far the preferential uptake of different components of mixed solvents by porous nanoparticles is not measured due to a lack of methods capable of detecting the resulting change in physical properties. Here, a new method, nanomechanical mass correlation spectroscopy, is used to reveal an unexpected dependence of the effective mass density of porous metal–organic framework (MOF) nanoparticles on the chemistry of the solvent system and on the chemical functionalization of the MOF's internal surface. Interestingly, the pore size of the nanoparticles is much too large for the exclusion of small solvent molecules by steric hindrance. The variation of effective density of the nanoparticles with the solvent composition indicates that a complex solvent environment can form within or around the nanoparticles, which may substantially differ from the solvent composition.</p

Mass Measurements Reveal Preferential Sorption of Mixed Solvent Components in Porous Nanoparticles

The interplay of physical and chemical properties at the nanometer scale provides porous nanoparticles with unique sorption and interaction capabilities. These properties have aroused great interest toward this class of materials for application ranging from chemical and biological sensing to separation and drug delivery. However, so far the preferential uptake of different components of mixed solvents by porous nanoparticles is not measured due to a lack of methods capable of detecting the resulting change in physical properties. Here, a new method, nanomechanical mass correlation spectroscopy, is used to reveal an unexpected dependence of the effective mass density of porous metal–organic framework (MOF) nanoparticles on the chemistry of the solvent system and on the chemical functionalization of the MOF's internal surface. Interestingly, the pore size of the nanoparticles is much too large for the exclusion of small solvent molecules by steric hindrance. The variation of effective density of the nanoparticles with the solvent composition indicates that a complex solvent environment can form within or around the nanoparticles, which may substantially differ from the solvent composition.</p

Multifunctional efficiency: extending the concept of atom economy to functional nanomaterials

Green chemistry, in particular, the principle of atom economy, has defined new criteria for the efficient and sustainable production of synthetic compounds. In complex nanomaterials, the number of embedded functional entities and the energy expenditure of the assembly process represent additional compound-associated parameters that can be evaluated from an economic viewpoint. In this Perspective, we extend the principle of atom economy to the study and characterization of multifunctionality in nanocarriers, which we define as “multifunctional efficiency”. This concept focuses on the design of highly active nanomaterials by maximizing integrated functional building units while minimizing inactive components. Furthermore, synthetic strategies aim to minimize the number of steps and unique reagents required to make multifunctional nanocarriers. The ultimate goal is to synthesize a nanocarrier that is highly specialized but practical and simple to make. Owing to straightforward crystal engineering, metal–organic framework (MOF) nanoparticles are an excellent example to illustrate the idea behind this concept and have the potential to emerge as next-generation drug delivery systems. Here, we highlight examples showing how the combination of the properties of MOFs (e.g., their organic–inorganic hybrid nature, high surface area, and biodegradability) and induced systematic modifications and functionalizations of the MOF’s scaffold itself lead to a nanocarrier with high multifunctional efficiency.</p

Multifunctional efficiency: extending the concept of atom economy to functional nanomaterials

Green chemistry, in particular, the principle of atom economy, has defined new criteria for the efficient and sustainable production of synthetic compounds. In complex nanomaterials, the number of embedded functional entities and the energy expenditure of the assembly process represent additional compound-associated parameters that can be evaluated from an economic viewpoint. In this Perspective, we extend the principle of atom economy to the study and characterization of multifunctionality in nanocarriers, which we define as “multifunctional efficiency”. This concept focuses on the design of highly active nanomaterials by maximizing integrated functional building units while minimizing inactive components. Furthermore, synthetic strategies aim to minimize the number of steps and unique reagents required to make multifunctional nanocarriers. The ultimate goal is to synthesize a nanocarrier that is highly specialized but practical and simple to make. Owing to straightforward crystal engineering, metal–organic framework (MOF) nanoparticles are an excellent example to illustrate the idea behind this concept and have the potential to emerge as next-generation drug delivery systems. Here, we highlight examples showing how the combination of the properties of MOFs (e.g., their organic–inorganic hybrid nature, high surface area, and biodegradability) and induced systematic modifications and functionalizations of the MOF’s scaffold itself lead to a nanocarrier with high multifunctional efficiency.</p

Exosome-coated metal–organic framework nanoparticles: an efficient drug delivery platform

Drug delivery systems aim at a reduction of side effects in chemotherapy. This is achieved by encapsulation of drugs in nanocarriers followed by controlled release of these drugs at the site of the diseased tissue. Though inorganic or polymeric nanoparticles (NPs) are often used as nanocarriers,(1, 2) hybrid nanomaterials such as metal?organic framework (MOF) NPs have recently emerged as a valuable alternative.(3-6) They are synthesized from inorganic and organic building block units to create porous three-dimensional frameworks. Because of this building principle, the composition and structure of these materials are highly tunable.(7-10) Furthermore, both external and internal surfaces can be functionalized independently. With these properties, MOF NPs can be designed to fit the specific requirements of the desired application.(3, 11) For drug delivery purposes these so-called “design materials” have been synthesized with high porosity allowing for high drug loading capacities. They also have been designed to be biodegradable. Specifically, iron-based MOF NPs have attracted great attention. In addition to the above-mentioned properties, they can be detected via magnetic resonance imaging (MRI), rendering them an ideal platform for theranostics.(12-14) In our study, we focus on one of these iron-based MOFs, namely MIL-88A NPs, which are composed of iron(III) and fumaric acid.(15, 16) Both compounds can be found in the body and the NPs are reported to be nontoxic.(12) Additionally, MIL-88A NPs have been shown to efficiently host chemotherapeutic drugs.(12) Thus, they represent a promising nanocarrier.</p

Exosome-coated metal–organic framework nanoparticles: an efficient drug delivery platform

Drug delivery systems aim at a reduction of side effects in chemotherapy. This is achieved by encapsulation of drugs in nanocarriers followed by controlled release of these drugs at the site of the diseased tissue. Though inorganic or polymeric nanoparticles (NPs) are often used as nanocarriers,(1, 2) hybrid nanomaterials such as metal?organic framework (MOF) NPs have recently emerged as a valuable alternative.(3-6) They are synthesized from inorganic and organic building block units to create porous three-dimensional frameworks. Because of this building principle, the composition and structure of these materials are highly tunable.(7-10) Furthermore, both external and internal surfaces can be functionalized independently. With these properties, MOF NPs can be designed to fit the specific requirements of the desired application.(3, 11) For drug delivery purposes these so-called “design materials” have been synthesized with high porosity allowing for high drug loading capacities. They also have been designed to be biodegradable. Specifically, iron-based MOF NPs have attracted great attention. In addition to the above-mentioned properties, they can be detected via magnetic resonance imaging (MRI), rendering them an ideal platform for theranostics.(12-14) In our study, we focus on one of these iron-based MOFs, namely MIL-88A NPs, which are composed of iron(III) and fumaric acid.(15, 16) Both compounds can be found in the body and the NPs are reported to be nontoxic.(12) Additionally, MIL-88A NPs have been shown to efficiently host chemotherapeutic drugs.(12) Thus, they represent a promising nanocarrier.</p