Unprecedented Contrast Agent to Measure the Age of Skin
- The fluorescent dye ElaNIR (Elastin Near-InfraRed) compares the functional age of skin,
blood vessel inner walls and internal organs of young and old mice -
Wrinkled sagging skin is probably the most visible sign of aging, but hidden within the body, blood vessel walls loose elasticity too, becoming more vulnerable to hypertension. The two processes are partly due to decreases of the same protein as people and animals age. A team of researchers at the Center for Self-Assembly and Complexity, within the Institute for Basic Science (IBS) have synthesized the first contrast agent to observe and measure elastin, the protein that gives strength to blood vessel walls, and flexibility to skin. Beyond cosmetics, the dye could be useful to better understand the role of elastin in biological processes and to verify the health of blood vessels and organs. The full study can be read in Chem.
“Since elastin is located in the subcutaneous tissue, it is difficult to visualize with current methods. Moreover, it is a complex protein to work with as it has various forms, variable chemical linkages, and it is renownedly difficult to make a model for computational study. For the screening, we used intact elastin from throughout the whole body to avoid such problems,” explains CHANG Young-Tae, corresponding author of the study.
The research team developed the first near-infrared fluorescent contrast agent for elastin, called ElaNIR (Elastin Near-InfraRed), capable of detecting the elasticity of tissues in living animals. The method is based on near-infrared rays with wavelengths of 700-900 nanometers which can reach elastin because of their excellent skin permeability. Moreover, ElaNIR was selected from a collection of fluorescence molecules that emit near-infrared rays. Generally, fluorescent materials tend to stick to other substances, resulting in a blurred image area around the target. On the other hand, ElaNIR has an equal number of positive and negative charges within the same molecule, which has been shown to minimize non-specific binding to serum proteins, normal tissues, and organs, which provides cleaner images.
ElaNIR not only emits fluorescence at the near-infrared range, but also allows to visualize elastin-containing structures via photoacoustic spectroscopy. In photoacoustic imaging, the absorbed light energy is converted into ultrasonic sound, which can penetrate skin better than fluorescence. As a result, photoacoustics can provide higher sensitivity and higher spatial resolution in ElaNIR compared to fluorescence imaging. Thanks to this technique, the scientists were able to acquire 3D tomographies by detecting ultrasonic waves generated by absorbed near-infrared light.
IBS scientists demonstrated the selective binding of ElaNIR to elastin using the cross section of a rabbit’s aorta. Then, they applied it to study mouse organs with high elastin content. ElaNIR was able to highlight elastin in lungs, skin, urinary bladder, kidney, aorta, and ears.
▲ Figure 1: ElaNIR screening and chemical structure. A) ElaNIR is a member of a library of fluorescent dyes that can emit near-infrared rays. It is a neutral molecule with two positive and two negative chemical groups. This features guarantees that it does not bind aspecifically to other biological molecules. B) ElaNIR highlights elastic layers, known as lamellae, in a rabbit’s aorta.
▲ Figure 2: Studying mouse organs with high elastin content, such as: kidney (A), aorta (B) and ears (C). ElaNIR (red) stains elastin (green), while Hoechst is specific for DNA.
Finally, ElaNIR was tested on living animals. When injected intravenously in old and young mice, the team was able to compare the amount of elastin in the skin. In the older rodents the amount of elastin was significantly reduced (1.8 times) compared to the younger ones. Using the photoacoustic technique, a high resolution 3D tomographic image was obtained which visually shows the distribution of elastin. Another promising feature of ElaNIR is its rapid removal from the system: more than 90% of the injected dose was cleared from the blood in four hours.
▲ Figure 3: ElaNIR shows differences in elastin concentration and distribution between young and old mice. (A) One-month old mice have higher concentrations of elastin on the skin than their 10-month old counterparts. (B) Elastin is also more concentrated in the internal organs of the younger mice, as shown in photoacoustic images captured in vivo (Li: liver, Sp: spleen, and Ki: kidney). (C) 3D tomographic reconstructions of the skin for the two types of mice. (D) Photoacoustic imaging (PAI) and fluorescence imaging (FI) of ElaNIR signal for younger and older mice are comparable.
"All current techniques estimate the age of the skin indirectly, for example via skin moisture. This is the first probe to directly measure skin elastin in living organisms, both painlessly and without biopsy," concludes Chang.
ElaNIR will be provided free of charge to researchers seeking opportunities for collaboration or application.
Letizia Diamante
Notes for editors
- References
- Dongdong Su, Chai Lean Teoh, Sung-Jin Park, Jong-Jin Kim, Animesh Samanta, Renzhe Bi, U. S. Dinish, Malini Olivo, Marie Piantino, Fiona Louis, Michiya Matsusaki, Seong Soon Kim, Myung Ae Bae and Young-Tae Chang. Seeing Elastin: A Near-Infrared Zwitterionic Fluorescent Probe for In Vivo Elastin Imaging. Chem (2018). DOI: 10.1016/j.chempr.2018.02.016
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- About the Institute for Basic Science (IBS)
IBS was founded in 2011 by the government of the Republic of Korea with the sole purpose of driving forward the development of basic science in South Korea. IBS has launched 28 research centers as of March 2018. There are nine physics, one mathematics, six chemistry, eight life science, one earth science, and three interdisciplinary research centers.