Nanoparticles shine through tissue

New imaging technology could help clinicians see tumors more clearly

A team of scientists, led by researchers from UMass Medical School, is developing novel biocompatible nanoparticles that can both absorb and emit near-infrared light through tissue. These particles could be attached to anomalies beneath the skin and used with deep tissue imaging, providing clinicians a new tool to see and diagnose tumors more clearly from the outside.

“I can foresee their utilization as analytical sensors for biomarkers or diagnosis in just a few years,” said Gang Han, PhD, assistant professor of biochemistry & molecular pharmacology and lead investigator on the study published in ACS Nano. “Though there are definitely some barriers to overcome, I do see great potential with respect to these special probes as to usage in the medical field and believe these agents will ultimately find their way into doctor’s offices.”

Composed of a crystalline core containing thulium, sodium, ytterbium and fluorine, encased inside a square, calcium-fluoride shell, the nanoparticles use a process known as near-infrared-to-near-infrared up-conversion (NIR-to-NIR) to help produce high-contrast bioimages. Through the NIR-to-NIR process, the particles absorb pairs of photons and combine them into a single, higher energy photon that it then emits, which is unnatural in biology.

Because the near-infrared region of the electromagnetic spectrum is the one at which biological tissue absorbs and scatters light the least, the concentrated light emitted by the nanoparticles has little competition from background noise. As a result, these emissions can potentially provide sharper images from deeper depths than traditional fluorescence-based imaging techniques. Physicians could use the nanoparticles to check disease development or diagnose tumors deep beneath the skin and deep tissue.

“These particles are special because they both absorb and emit near-infrared light with the emitted light having a shorter wavelength,” said Dr. Han. “This is important because it’s different from how molecules in biological tissues absorb and emit light. As a result, the light emitted from the nanoparticle can be more readily distinguished from nearby biological tissues, giving us higher-contrast images.”

And because calcium-fluoride is common in bones and teeth, its inclusion in the shell of the novel nanoparticles makes it biocompatible within the body.

So far, the scientists have injected the nanoparticles into animal models and a three-centimeters-thick slice of pork. In both cases, Han and colleagues were able to obtain “vibrant, high-contrast images of the particles shining through tissue,” he said.

Before advancing to the clinic though, Han cautions that a complete biocompatibility and toxicity profile will need to be done. At the same time, medical devices adapted to the unique optical properties of the nanoparticles will need to be built.

Han and colleagues are now working to develop methods of attaching these particles to various therapeutics (e.g., siRNA, proteins, small molecule drugs, stem cells) to precisely record their in vivo traffickings and the concomitant treatment responses that were either unseen or blurred using existing tools.

“(α-NaYbF(₄):Tm(³⁺))/CaF(₂) Core/Shell Nanoparticles with Efficient Near-Infrared to Near-Infrared Upconversion for High-Contrast Deep Tissue Bioimaging” by Guanying Chen, Jie Shen, Tymish Y. Ohulchanskyy, Nayan J. Patel, Artem Kutikov, Zhipeng Li, Jie Song, Ravindra K. Pandey, Hans Ågren, Paras N. Prasad, and Gang Han appears in ACS Nano, one of the top scientific journals in the nanoscience field.