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Human-made nanocrystals can now be attached to antibodies, supercharging them with drugs that can target diseased cells with unreal precision, leaving the rest alone — meaning fewer side effects. Antibodies already know where to go, and the crystal can then work its magic. This could mean unprecedented treatments for cancer as well as cardiovascular and autoimmune diseases.
This is a type of metal-organic framework, or MOF. Zinc joins forces with carbonate ions and an imidazole (a colorless organic molecule that dissolves in water) to carry medication where it is needed. MOF crystals then break down low PH when they bind to diseased cells, releasing invaluable medicine. Researcher Christoph Hagemeyer of Monash University in Australia collaborated with a team from TU Graz in Austria and coauthored a study, recently published in Advanced Materials, on this breakthrough.
“Metal-organic frameworks have been around for quite some time but what is novel about our system is that this MOF likes to be decorated with oriented antibodies, a major class of human therapeutics and diagnostics,” Hagemeyer told SYFY WIRE.
What may be unexpected about this sci-fi sounding technology is how simple it is. Zinc, imidazole, water, and CO2 from the air are all that is needed to create a crystal that can encapsulate and carry a surprisingly large payload of substances right to the cells that need them. This MOF’s precision comes from positively charged zinc ions (cations), negatively charged carbon ions (anions) from CO2, and a specific kind of imidazole known as 2-methylimidazole. It can take on much more therapeutic or diagnostic cargo than earlier MOFs.
So how does this almost supernatural crystal stay attached for the ride? When zinc, imidazole, and carbonate merge on an antibody, the crystal forms on a specific part of that antibody. This is the constant region. Antibodies themselves are actually proteins in the immune system, Y-shaped molecules otherwise known as immunoglobulins. The constant region determines how an antibody will destroy an antigen, the villain that causes poisoning or disease, when it binds to that antigen. The production of antibodies is switched on by the body when antigens invade.
“The constant region is opposite the antigen binding part of the antibody, so it can still target while carrying a large load of drugs,” Hagemeyer said. “This is unprecedented; in the past, trying to attach more drugs to an antibody negatively impacted its ability to bind to a target.”
With regards to the MOF’s disease-fighting powers, not only can it pack in a remarkable amount of molecules (current antibody systems can only fit 3-5 molecules), but the treatment loaded onto it can also be personalized to fit the patient’s specific condition and body chemistry. What decimates cancer in one person may not necessarily do so for another. Antibodies themselves can also navigate to a target more precisely than anything else, so binding the crystal to an antibody means that it is unlikely to have a negative impact on healthy surrounding tissues.
Because the new MOF is not only potent but also effectively protects the payload of diagnostics or therapeutics it carries, it will be ideal for patients who may not live anywhere near sprawling cities with gleaming, state-of-the-art hospitals that are always having new wings added and networks of doctors who are always available. It may be an equalizer. Hagemeyer believes that something this portable could make the trip to more remote areas and revolutionize the way medical care is carried out and make powerful treatments accessible for many more patients.
“This combination of properties holds much promise for customized drug delivery systems that can be prepared at the point-of-care,” he said. “The system is also highly suitable to serve patients living where there is less medical infrastructure compared to large cities.”
This is unprecedented in the field, as in the past when trying to attach more and more drug to an antibody negatively impacts the ability to bind to its target. Our system overcomes this limitation.