Stable doesn’t mean safe: What happens to MOFs inside living systems

Imagine a sponge so small you cannot see it, yet so precisely built that it can; trap gases; clean polluted water; or carry medicines inside the body. That, in simple terms, is what a metal–organic framework (MOF) is. MOFs are built by linking metal atoms with organic molecules to form tiny, orderly cages with an enormous internal surface area - which is why they are often called ‘wonder materials’.

But there is an uncomfortable truth behind the excitement: we still do not fully understand what happens to these materials once they leave the laboratory.

Much of the confidence in MOFs comes from stability. In many tests, some MOFs can sit in water, tolerate heat, and survive harsh chemical conditions without visibly falling apart. This has encouraged a simple assumption: if a material is stable in the environment, it must also be safe and stable in the body. That assumption is wrong.

Here is the key point in plain language: a material can look rock-solid in non-living (abiotic) conditions - like air, clean water, or laboratory solutions - and still break down quickly inside a living organism. ‘Stable in the environment’ does not automatically mean ‘stable in life’.

To show this clearly, we used UiO-66, a well-known zirconium-based MOF that is widely reported as one of the most stable MOFs. In other words, if any MOF should stay intact, UiO-66 is a strong candidate - which makes it an ideal case study.

In our recent work, we followed UiO-66 as it moved through a realistic sequence of settings: air, water, and then a living organism. In air and water, UiO-66 behaved largely as expected. It stayed mostly intact. Nothing dramatic happened. If we had stopped there, we might have concluded that the material poses little risk.

But biology changed everything.

When UiO-66 was eaten by a tiny freshwater animal called a water flea (Daphnia Magna) - an organism that plays a key role in aquatic ecosystems - the framework broke down rapidly inside the gut. It did not simply pass through unchanged. Instead, it was chemically transformed into new forms. Even more concerning, the animals did not immediately die, but their ability to reproduce was strongly reduced. The effect was subtle and delayed - the kind of harm that can be missed if we only focus on short-term survival tests.

This exposes a major gap in how we often evaluate new materials.

We tend to test materials ‘one environment at a time’: in a bottle of water, under light, or in clean laboratory air. These tests are useful, but they can give a false sense of safety because they ignore how materials actually travel through the world. In reality, materials move from air into water, from water into sediment or soil, and from there into living organisms. Each step changes the rules. The body, especially, is not a passive container. It is a chemically active place filled with acids, enzymes and natural binding molecules that can pull materials apart - even materials that appear extremely stable outside life.

This does not mean MOFs are bad or should be abandoned. Their tunability is exactly what makes them promising. But it does mean we must design them more thoughtfully. ‘Stability’ should not be treated as one universal badge of safety. A material might need to stay intact during use - but it should also be able to break down safely afterwards, into forms that do not persist or cause harm. That is not a flaw. That is good design.

Medicine already works this way. Drug carriers are often designed to stay intact in the bloodstream but fall apart inside a cell or a tumour where they are needed. Environmental technologies deserve the same level of care: performance where you want it, and safe breakdown where you do not.

MOFs are powerful tools. But power without understanding creates risk. If we keep equating “stable” with “safe”, we will keep missing the most important transformations of all - the ones that happen quietly inside living systems, long after the excitement of discovery has faded.