A team of researchers has achieved a long-sought goal of creating nanoparticles that can emit a colorful fluorescent glow in a biological environment and also be precisely manipulated into position within living cells.

The new technology, reported this week in the journal Nature Communications, could make it possible to track the position of the nanoparticles as they move within the body or inside a cell and also manipulate them precisely by applying a magnetic field to pull them along.

In addition, the particles could have a coating of a bioreactive substance that could seek out and bind with particular molecules within the body, such as markers for tumor cells or other disease agents.

Combining fluorescence and magnetism

“It’s been a dream of mine for many years to have a nanomaterial that incorporates both fluorescence and magnetism in a single compact object,” says Moungi Bawendi, the Lester Wolfe Professor of Chemistry at MIT and senior author of the new paper. While other groups have achieved some combination of these two properties, Bawendi says that he “was never very satisfied” with results previously achieved by his own team or others.

He says such particles have been too large to make practical probes of living tissue and not of uniform and predictable size.

“We wanted to be able to manipulate these structures inside the cells with magnetic fields, but also know exactly what it is we’re moving,” says Bawendi.

All of these goals are achieved by the new nanoparticles, which can be identified with great precision by the wavelength of their fluorescent emissions.

The new method produces the combination of desired properties “in as small a package as possible,” Bawendi says — which could help pave the way for particles with other useful properties, such as the ability to bind with a specific type of bioreceptor, or another molecule of interest.

In the new method, the nanoparticles crystallize such that they self-assemble in exactly the way that leads to the most useful outcome: The magnetic particles cluster at the center, while fluorescent particles form a uniform coating around them. That puts the fluorescent molecules in the most visible location for allowing the nanoparticles to be tracked optically through a microscope.

Initially, at least, the particles might be used to probe basic biological functions within cells, Bawendi suggests. As the work continues, later experiments may add additional materials to the particles’ coating so that they interact in specific ways with molecules or structures within the cell, either for diagnosis or treatment.

The ability to manipulate the particles with electromagnets is key to using them in biological research, Bawendi explains: The tiny particles could otherwise get lost in the jumble of molecules circulating within a cell. “Without a magnetic ‘handle,’ it’s like a needle in a haystack,” he says. “But with the magnetism, you can find it easily.”

A silica coating on the particles allows additional molecules to attach, causing the particles to bind with specific structures within the cell. “Silica makes it completely flexible; it’s a well developed material that can bind to almost anything,” Bawendi says.

For example, the coating could have a molecule that binds to a specific type of tumor cells; then, “You could use them to enhance the contrast of an MRI, so you could see the spatial macroscopic outlines of a tumor,” he says.

Testing in biological settings

The next step for the team is to test the new nanoparticles in a variety of biological settings. “We’ve made the material,” Chen says. “Now we’ve got to use it, and we’re working with a number of groups around the world for a variety of applications.”

Christopher Murray, a professor of chemistry and materials science and engineering at the University of Pennsylvania who was not connected with this research, says, “This work exemplifies the power of using nanocrystals as building blocks for multiscale and multifunctional structures.”

The study included researchers at MIT; Massachusetts General Hospital; Institut Curie in Paris; the Heinrich-Pette Institute and the Bernhard-Nocht Institute for Tropical Medicine in Hamburg, Germany; Children’s Hospital Boston; and Cornell University. The work was supported by the National Institutes of Health, the Army Research Office through MIT’s Institute for Soldier Nanotechnologies, and the Department of Energy.

MIT | Controllable nanoparticles

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Abstract of Magneto-fluorescent core-shell supernanoparticles

Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle ‘core’, which is fully surrounded by a ‘shell’ of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. We demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.