A Sandia National Laboratories team has designed and synthesised nanoparticles that glow red and are stable, useful properties for tracking cancer growth and spread. This work is the first time the intrinsic luminescence of metal-organic framework materials, or MOFs, for long-term bioimaging has been reported, materials chemist Dorina Sava Gallis said. Fluorescently-tagging tumours, or other specific kinds of cells, is a new, powerful method to image inside a body.
MRIs, X-rays and ultrasounds are powerful bioimaging methods to diagnose diseases. However, these methods each have their limitations and generally aren’t used to treat diseases. For years, scientists have been searching for theranostic agents, materials that have both therapeutic and diagnostic uses.
MOFs are one group of chemicals with great potential for imaging and treating cancer and other diseases. These tinker toy-like molecules have metal “hubs” and carbon-based linker 'rods.'
Chemists can swap out the hubs and the linkers to make nanosized 'sponges' with many different properties. Historically, MOFs have been used for everything from capturing radioactive gases from spent nuclear fuel, to cleaning contaminated water and even storing hydrogen gas safely.
The Sandia team’s MOF nanoparticles glow red or near infrared for at least two days in cells.
Near infrared light has longer wavelengths than red light. It is especially useful for imaging inside a body because it can penetrate skin, tissue and even bone without causing damage, and produces clearer images because there’s less background autofluorescence at those wavelengths, said Sava Gallis.
Current dyes or nanoparticles that glow in the near infrared don’t last for very long or only glow weakly, making brighter, more stable materials invaluable.
MOFs are complex materials with tunable properties and astonishing surface areas; one gram of a certain kind of MOF has the same surface area as 16 basketball courts. Sava Gallis said, “In the field of metal-organic frameworks, we have the advantage of choosing our building blocks to make made-to-order materials.”
For 14 years, she has been working on making the synthesis of MOFs more rational and predictable. Some metals are chemically active and others glow at certain colors. Some metals form clusters with different geometries — like tinker toy “hubs” with different numbers of holes — and sometimes the hub is a single metal ion.
Some linkers are long, producing sponges with large empty spaces and high surface areas, and others are short. Some linkers are catalytically active — that is, they can speed up a chemical reaction — or can tweak the chemistry of the metal while others can adjust the color or brightness of the metal’s glow.
To rationally design MOFs for bioimaging, Sava Gallis selected lanthanide metals, a class of rare earth elements. The metal europium glows red; the metals neodymium and ytterbium fluoresce in the near infrared.
She also chose conditions that would cause the lanthanides to form robust clusters. Frequently, MOFs made with individual metal ions aren’t water-stable, but metal clusters often are, said Sava Gallis.
This is important for bioimaging as cells and people are mostly water. Also, she used commonly available carbon linkers that produce large pores. Potentially, these pores could hold drugs and allow both imaging and treatment.
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Image credit: Sandia National Laboratories.