Imagine a tiny sponge that weighs as much as a couple of sugar cubes, but that contains so many itty bitty pores that its surface area equals that of a football field.
What if scientists could engineer the sponge to serve a variety of therapeutic purposes, including storing drugs and enhancing cancer therapies? Such sponges exist, in a class of ultra-porous crystals known as metal-organic frameworks, or MOFs.
Research into potential uses for MOFs has accelerated over the past five years, chemists said. They predict the crystalline compounds could transform healthcare, energy and other industries. Some said MOFs could become as widespread as polymers, compounds that form the basis of many man-made materials like plastics, in the next decade or two.
“MOFs are the compound of the future,” said M. Raza Shah, a professor of chemistry at the International Center for Chemical and Biological Sciences in Karachi, Pakistan.
MOFs have two components: a metal and an organic compound, which in chemistry refers to materials that contain carbon. Sometimes compared to Tinkertoys, each MOF crystal resembles a three-dimensional scaffolding made up of metal nodes connected by organic rods.
The nodes and rods form a regular network of spaces, where materials like gases and drug molecules can be captured, stored and separated. The spaces are what give MOFs their sponge-like quality and are a big part of what makes them special, chemists said, because each MOF crystal has a staggering number of them. A MOF crystal the size of a grain of sand could have upward of thousands of millions of spaces, chemists said. The current record for MOF storage capacity is 7,000 square meters per gram. A tiny amount of MOF could pack a huge punch.
Researchers are exploring how to use MOFs’ super-porosity in medicine and other fields. Cancer therapies are one area where MOFs have shown significant potential, said Wenbin Lin, a chemist at the University of Chicago. In 2018, Dr. Lin helped start a phase I clinical trial to assess whether MOFs could enhance the benefits of radiotherapy in patients with advanced-stage cancer.
Radiation therapy kills cancer cells and can shrink tumors, but the radiation is toxic to normal cells too and can cause side effects. Dr. Lin and his collaborators created MOFs that absorb and amplify radiation. Made with the metal hafnium and an organic compound that Dr. Lin says is proprietary, the MOFs were injected into cancerous tumors, which were then treated with radiation therapy. The structure of the MOFs allows them to trap secondary particles and photons from the radiation, Dr. Lin said. The idea is that the MOFs can enhance the effect of the radiation in tumor cells without amplifying damage to normal cells.
Thanks to their super-porosity, only a small number of MOFs is needed to be injected into each tumor, Dr. Lin said. The MOFs eventually break down harmlessly in the body, he said.
Results from the completed trial haven’t been released. Dr. Lin said preliminary analyses show that patients treated with the MOFs could be exposed to half the amount of radiation and achieve a better tumor-shrinking effect. He added that the MOFs appeared to be well-tolerated by patients.
“I’m very hopeful that this will provide a totally new way of treating cancer patients,” Dr. Lin said.
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At the University of Glasgow in Scotland, chemist Ross Forgan has been conducting laboratory experiments to explore how MOFs could be used to deliver potent drugs directly into cancer cells, potentially increasing uptake and mitigating some side effects. He said some cancer drugs have shown potential at eradicating cancer cells but have trouble penetrating the cell membrane.
“We can tune the MOF to make it more able to enter the cell,” Dr. Forgan said. To deliver a certain drug into cancer cells, Dr. Forgan and his colleagues designed a MOF filled with the drug and coated with a fat-soluble chemical that can penetrate cancer-cell membranes, which are made up of fat layers. A study co-authored by Dr. Forgan found that when the MOF was used for delivery, a much smaller amount of the drug was needed to produce effects similar to when the drug was used alone.
Scientists are experimenting in laboratory experiments with luminescent MOFs, said Masoud Mozafari, a biomedical engineer at the University of Toronto. While such MOFs have yet to be used for biomedical purposes, they could be designed to be attracted to certain biomarkers or cells, Dr. Mozafari said. By injecting these glowing MOFs into the body, diseases like cancer could be detected at an early stage, he added.
Hafnium, zirconium, iron and zinc are among the metals commonly used in MOFs designed for biomedical applications. Small amounts of the metals aren’t toxic, say chemists working on these compounds, but large quantities could cause poisoning. Some organic compounds and solvents can also be harmful.
MOFs for biomedical use would ideally be non-toxic at therapeutic doses and stable enough to do their job before breaking down naturally. Dr. Lin said it took him the better part of two decades to figure out how to design MOFs for therapeutic purposes.
Tina Nenoff, a senior scientist at Sandia National Laboratories, a federally funded research laboratory that specializes in national security, said MOFs can be expensive to make, particularly when they include costly metals like zinc or gold. As technology improves and more MOFs are created, she said she expected costs to drop.
Dr. Nenoff is exploring how MOFs could be used as sensors to detect toxic gases or to separate one gas from another. The Department of Energy and Department of Defense have funded research into these sensors, Dr. Nenoff said, which she noted could one day be used by the U.S. military to detect the chemicals that aging munitions emit into the environment, among other uses.
“Depending on how you design them, how you decorate them, you can make MOFs very selective for almost any application,” said Dr. Nenoff.
MOFs have also shown promise in antimicrobial treatments and tissue regeneration. Researchers including Dr. Forgan have designed MOFs that neutralize pathogens and have implanted them in face-mask filters and the lining of catheters. These devices remain in the prototype phase.
Researchers are also leveraging MOFs for carbon capture and water filtration. Companies including Exxon Mobil Corp., Saudi Arabian Oil Co. and
have invested in research into MOFs’ potential uses.
NuMat Technologies, an Illinois-based startup that became one of the first companies to commercialize MOFs in 2016, sells MOFs that store toxic chemicals used in the electronics industry.
“Almost every sector of the economy has use for MOFs,” said Omar Yaghi, a chemist at the University of California, Berkeley, who is widely acknowledged as having coined the term MOFs and was among the first to make the compounds.
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