Nanoluminous pearls developed by scientists at UMMS

A microscopic crystal created by researchers at UMass Medical School brings the potential use of persistent luminescence nanoparticles for bioimaging one step closer to both the research laboratory and the clinic. The successful development of these long-lasting, light-emitting nanocrystals would provide much improved, noninvasive imaging technology for evaluating structural and functional biological processes in living animals and patients.

Compared to existing in vivo optical imaging probes, these new nanoparticles possess an outstanding signal-to-noise-ratio with no need for an excitation resource (light) during imaging and they can be directly detected with existing imaging systems. Published in the Journal of the American Chemical Society, the study was selected as an editor’s choice and a spotlight article.

“Ultra-small luminescent phosphors are playing an increasingly vital role in medicine and science,” said Gang Han, PhD, assistant professor of biochemistry & molecular pharmacology and principal investigator of the study. “Our straightforward method for producing these tiny near-infrared persistent luminescence nanoparticles, coupled with their superior performance and luminescence renewability, is groundbreaking. It opens up opportunities for developing a new generation of technologies to use in medical imaging diagnosis and therapy, as well as other applications in photonics and biophotonics.”

Persistent luminescence is the term given to materials that continue to emit light for minutes or hours, and in some cases day, after turning off the excitation source. These materials have been used by humans for 1,000 years and are common today in traffic signs, emergency signage, watches and clocks, luminous paints, electronic displays and textile printing.

Biomedical researchers are striving to develop similar persistent luminescence nanoparticles that are safe to inject into live biological tissues for imaging. A persistent luminescence material that can last for hours or days combined with current imaging technologies such as magnetic resonance imaging (MRI), micro-computed tomography (micro CT), positron emission tomography (PET), optical coherence tomography (OCT), electron tomography (ET), ultrasonic imaging and X-ray imaging, could greatly improve diagnostic capabilities available to both biomedical researchers and physicians.

Current methods for producing these light-emitting particles are complex. They require synthesis with extremely high temperature annealing (>1,000°C) and a complicated physical process to transform large, bulk crystals into nanoparticles. This often creates heterogeneous particles that quickly agglomerate in solution and are too large for use in biological tissues, as their size could potentially disrupt cellular systems and cause harm.

Using a new production methodology, Dr. Han and colleagues have overcome this key developmental roadblock. The resulting nanocrystals were dubbed “luminous pearls” by Han after the legendary Chinese tale of the seven fairies, which used luminous pearls to store the daytime sunlight, and then released it “to weave the rose clouds of the dawn.”

“This image is particularly apt, because the methods described in the paper produce near-infrared luminescence nanoparticles that in effect have renewable luminescence,” said Han.

The new aqueous production method described in the research paper uses a convenient chemical approach to generate ultra small and uniform nanoparticles the size of a protein. Han and colleagues used hydrothermal synthesis, making use of the chemical reactions of substances in a sealed heated aqueous solution to produce zinc-gallium-chromium nanoparticles. During this process, they found that the molar ratio of zinc to gallium was the secret to producing uniformly ultrasmall, near-infrared persistent luminescence nanoparticles.

Measuring the performance of their “luminous pearls,” the researchers found that they provide vivid images through deep tissue of a live mouse after only a brief LED light irradiation prior to injection. This signal gradually decreased after 30 minutes and it could also be reactivated repeatedly at any desired time. The hydrothermally produced nanoparticles also showed good stability, which is necessary for biomedical applications. They remained viable for one month after insertion.

“It’s likely these hydrothermally produced nanocrystals are smaller but brighter than similar materials due to the fact that they have fewer defects, with more regular shapes and complete crystal facets. They can also be repeatedly recharged within deep tissues and have the potential to be directly adapted for use in commercially available imaging systems.” said Han.

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