Nanoparticles Glow through Thick Layer of Tissue
An international research team has created unique photoluminescent nanoparticles that shine clearly through more than three centimeters, or more than an inch, of biological tissue, a depth that makes them a promising tool for deep-tissue optical bioimaging. The newly created nanoparticles, developed by a team led by Gang Han of the University of Massachusetts Medical School and Paras Prasad of the University of Buffalo, consist of a nanocrystalline core containing thulium, sodium, ytterbium and fluorine, all encased inside a square, calcium-fluoride shell.
Though optical imaging is a robust and inexpensive technique commonly used in biomedical applications, current technologies lack the ability to look deep into tissue. This limitation has driven researchers to develop new approaches that provide high-resolution, high-contrast optical bioimaging that clinicians and scientists could use to identify tumors or other anomalies deep beneath the skin.
The nanoparticles, first developed by Dr. Gang and his collaborators, are special for several reasons. To begin with, they absorb and emit near-infrared (NIR) light, with the emitted light having a much shorter wavelength than the absorbed light. This is different from how molecules in biological tissues absorb and emit light, which means that scientists can use the particles to obtain deeper, higher-contrast imaging than traditional fluorescence-based techniques.
In addition, the material for the nanoparticle's shell – calcium fluoride – is a substance found in bone and tooth mineral. This makes the particles compatible with human biology, reducing the risk of adverse effects. The shell is also found to significantly increase the photoluminescence efficiency. These new particles are described in a paper published in the journal ACS Nano.
To emit light, the particles employ a process called near-infrared to near-infrared up-conversion, or "NIR-to-NIR." Through this process, the particles absorb pairs of photons and combine these into single, higher-energy photons that are then emitted. One reason NIR-to-NIR is ideal for optical imaging is that the particles absorb and emit light in the near-infrared region of the electromagnetic spectrum, which helps reduce background interference. This region of the spectrum is known as the "window of optical transparency" for biological tissue, since the biological tissue absorbs and scatters light the least in this range.
The scientists tested the particles in experiments that included injecting and imaging them in mice, and imaging a capsule full of the particles through a slice of animal tissue (pork) more than three centimeters thick. In each case, the researchers were able to obtain vibrant, high-contrast images of the particles shining through tissue. The next step in the research is to explore ways of targeting the nanoparticles to cancer cells and other biological targets.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, "(α-NaYbF4:Tm3+)/CaF2 core/shell nanoparticles with efficient near-infrared to near-infrared upconversion for high-contrast deep tissue bioimaging." Investigators from the Harbin Institute of Technology, Swedish Royal Institute of Technology, University of Massachusetts Medical School, the University of North Carolina at Chapel Hill, and Korea University contributed to this project. An abstract of this paper is available at the journal's website.