In the past few years, numerous studies have demonstrated the great potential of nano particles of metal-organic frameworks (nanoMOFs) at the preclinical level for biomedical applications. Many of them were reported very recently based on their bioactive composition, anticancer application, or from a general drug delivery/theranostic perspective. In this review, the authors aim at providing a global view of the studies that evaluated MOFs' biomedical applications at the preclinical stage, when in vivo tests are described either for pharmacological applications or for toxicity evaluation. The authors first describe the current surface engineering approaches that are crucial to understand the in vivo behavior of the nanoMOFs. Finally, after a detailed and comprehensive analysis of the in vivo studies reported with MOFs so far, and considering the general evolution of the drug delivery science, the authors suggest new directions for future research in the use of nanoMOFs for biomedical applications.
Despite high morbidity and mortality associated with lung diseases, addressing drugs towards lung tissue remains a pending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery. However, toxicity issues derived from the long-term presence of the particles must be overcome. By exploiting some of the ignored properties of nanosized metal-organic frameworks it is possible to achieve impressive antitumoral effects on experimental lung tumors, even without the need to engineer the surface of the material. In fact, it was discovered that, based on unique pH-responsiveness and reversible aggregation behaviors, nanoMOF was capable of targeting lung tissue. At the neutral pH of the blood, the nanoMOFs form aggregates with the adequate size to be retained in lung capillaries. Within 24 h they then disaggregate and release their drug payload. This phenomenon was compatible with lung tissue physiology.
In article number https://doi.org/10.1002/adma.201707365, Patrick Couvreur, Christian Serre, and co‐workers evaluate the biomedical applications of metal–organic frameworks at the preclinical stage, for pharmacological applications or toxicity evaluation. Current surface‐engineering approaches, in vivo studies, and their prospects are considered. The back cover image illustrates the circulation of drug‐loaded MOF nanoparticles in a blood vessel. In particular, nanosized cages of MIL‐100(Fe) loaded with Ibuprofen drug are represented. Cover project designed by Maria Mikołajczak‐Zygmańska.
Despite high morbidity and mortality associated with lung diseases,a ddressing drugs towards lung tissue remains ap ending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery.H owever,toxicity issues derived from the long-term presence of the particles must be overcome.Byexploiting some of the ignored properties of nanosized metal-organic frameworks it is possible to achieve impressive antitumoral effects on experimental lung tumors,e ven without the need to engineer the surface of the material. In fact, it was discovered that, based on unique pH-responsiveness and reversible aggregation behaviors,n anoMOF was capable of targeting lung tissue.A tt he neutral pH of the blood, the nanoMOFs form aggregates with the adequate sizetoberetained in lung capillaries.Within24h they then disaggregate and release their drug payload. This phenomenon was compatible with lung tissue physiology.
Among a plethora of drug nanocarriers, biocompatible nanoscale Metal Organic Frameworks (nanoMOFs) with large surface area and amphiphilic internal microenvironment have emerged as promising drug delivery platforms, mainly for cancer...
Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.
Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.
Biocompatible nanoscale iron carboxylate metal organic frameworks (nanoMOFs) already demonstrated their ability to efficiently deliver various therapeutic molecules. The versatility of the synthetic methods and functionalization strategies could further improve...
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