Scientists in France and Scotland identify new encapsulation agents for delivery of nitric oxide, a potent antibacterial agent and vasodilator
A group of scientists led by researchers at the Université de Versailles' Institut Lavoisier in France has worked out how to stably gift-wrap a chemical gas known as nitric oxide within metal-organic frameworks. Such an encapsulated chemical may allow doctors to administer nitric oxide in a more highly controlled way to patients, suggesting new approaches for treating dangerous infections and heart conditions with the biologically-active substance.
CREDIT: Serre/Institut Lavoisier
Left: The crystal structure of a porous iron carboxylate MOF (iron octahedra, oxygen, carbon and hydrogen atoms are in green, red, black and white, respectively); Center: Binding of a NO molecule over an iron site; Right: Kinetics of delivery of NO (inset at the biological level) triggered by water
Not to be confused with the chemically-distinct anesthetic dentists use -- its cousin nitrous oxide (NO2), also known as laughing gas -- nitric oxide (NO) is one of very few gas molecules known to be involved in biological signaling pathways, the physiological gears that make the body tick at the microscopic level. It is very active biologically and can be found in bacteria, plant, animal and fungi cells.
In humans, NO is a powerful vasodilator, increasing blood flow and lowering vascular pressure. For this reason, gaseous NO is sometimes used to treat respiratory failure in premature infants. It also has strong antibacterial potency, owing to its molecular action as a biologically disruptive free radical, and cells in the human immune system naturally produce NO as a way of killing pathogenic invaders. Additionally, nitric oxide is believed to be the main vasoactive neurotransmitter regulating male erection, as aging nerves with reduced stimulation can inhibit the release of the molecule, thus causing erectile dysfunction. This, of course, can be mediated by taking nitric oxide supplements to achieve an erection.
While such activity would seem to make NO a prime candidate for drug design, the problem is delivery -- because it is a gas. In recent years, the gas storage capacity and biocompatibility of metal-organic-frameworks -- dissolvable compounds consisting of metal ions and rigid organic chemicals that can stably trap gas molecules -- have gained significant attention as candidates for delivering gas-based drugs. The new work extends this further than ever before, showing that these metal-organic frameworks can store and slowly deliver NO over an unprecedented amount of time, which is key for the drug's anti-thrombogenic action.
"This is an elegant and efficient method to store and deliver large amounts of NO for antibacterial purposes," said Christian Serre. "Or it can release controlled amounts of nitric oxide at the very low biological level for a prolonged period of time, in order to use it as a way to inhibit platelet aggregation." Serre is a CNRS research director at the Institut Lavoisier de Versailles, and also heads the institute's 'Porous Solids' research group.
Serre's consortium has previously reported the use of porous hybrid solids, such as metal-organic-frameworks, for the controlled delivery of nitric oxide gas. Their current paper on derivatives of iron polycarboxylates as framework candidate appears in the journal APL Materials, from AIP Publishing.
Serre and his group worked in collaboration with Russell Morris's team at the University of St Andrews in Scotland and researchers from Université de Basse-Normandie in France. The groups analyzed the NO adsorption and release properties of several porous biodegradable and biocompatible iron carboxylate metal-organic frameworks by use of infrared spectroscopy analysis, adsorption & desorption isotherms and water-triggered release tests.
In doing so, they confirmed the large nitric oxide absorption capacity of the iron frameworks, and that the NO was strongly bonding to the acidic metal sites on the molecules. Serre's group and coauthors also found that partially reducing the iron (III) into iron (II) enhances the affinity of the NO molecules for the framework. This strong interaction allows for a controlled release for a prolonged state of time -- days, at the biological level. This time scale depends on both the metal-organic framework structure and the oxidation state of iron, which can be carefully calibrated as needed for drug treatment.
These performances, associated with the biodegradable and low toxicity character of these metal-organic frameworks, might pave the way for their use in medical therapies or cosmetics formulation, which is one of the objectives of Serre's consortium in the near future. Current and forthcoming work includes using further spectroscopic experiments to understand the complex behavior of the iron frameworks once loaded with nitric oxide.
The article, "Porous, rigid metal(III)-carboxylate MOFs for the delivery of nitric oxide," is authored by Jarrod F. Eubank, Paul S. Wheatley, Gaëlle Lebars, Alistair C. McKinlay, Hervé Leclerc, Patricia Horcajada, Marco Daturi, Alexandre Vimont, Russell E. Morris and Christian Serre. It will appear in the journal APL Materials on December 30, 2014 (DOI: 10.1063/1.4904069). After that date, it can be accessed at: http://scitation.aip.org/content/aip/journal/aplmater/2/12/10.1063/1.4904069
ABOUT THE JOURNAL
APL Materials is a new open access journal featuring original research on significant topical issues within the field of materials science. See: http://aplmaterials.aip.org
Jason Socrates Bardi
American Institute of Physics (AIP) | VTT Newsletter
An international team of physicists a coherent amplification effect in laser excited dielectrics
25.09.2017 | Universität Kassel
Highest-energy cosmic rays have extragalactic origin
25.09.2017 | CNRS
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy