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New dye allows visualization of deep tissue and facilitates cancer diagnosis and treatment

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Researchers from Tokyo Metropolitan University have developed a new dye capable of intensively absorbing second near-infrared radiation and converting it into heat. Taking a dye from the bile pigment family, they developed a unique ring structure capable of binding rhodium and iridium. Measurements and modeling showed strong absorption of second near-IR wavelengths and exceptional photostability. Second near-infrared wavelengths readily penetrate human tissues; the new dye may find applications in therapy and deep tissue imaging.

Infrared radiation is electromagnetic radiation that is at the boundary with the red spectrum of visible light. The human eye is unable to see this spectrum, but we can feel it as heat. When exposed to infrared rays, objects heat up. The shorter the wavelength of infrared radiation, the stronger the heat effect will be.

According to the International Organization for Standardization (ISO), infrared radiation is divided into three ranges: near, medium and far. Only the near infrared range is used in medicine because it does not scatter on the surface of the skin and penetrates subcutaneous structures

IR light therapy has shown high efficiency in the treatment of various diseases: pneumonia, influenza, angina, bronchial asthma, vasculitis, bedsores, varicose veins, heart disease, frostbite and burns, some forms of dermatitis, diseases of the peripheral nervous system and malignant skin neoplasms.

The second near-infrared region of the electromagnetic spectrum (1000-1700 nanometers) is a potentially important wavelength range for medicine. In this range, light is not as strongly scattered or absorbed by biological tissues. This transparency makes it ideal for delivering energy to deeper parts of the body for both imaging and treatment. An important example of this therapy is photoacoustic imaging in cancer diagnosis and treatment. When a contrast agent injected into the body is exposed to light, it emits heat that creates tiny ultrasonic discharges detectable for imaging or used to damage cancer cells.

The effectiveness of this approach depends on the availability of stable contrast agents that can effectively absorb light at these wavelengths. However, most contrast agents are more sensitive in the first near-infrared range (700-1000 nanometers), where scattering effects are stronger and energy delivery is less efficient.

Now a team of researchers led by Associate Professor Masatoshi Ichida of Tokyo Metropolitan University has developed a new chemical compound that eliminates this Achilles’ heel. Taking a dye from a family of bile pigments called bilatriene, they used a method known as N-confusion chemistry to alter the ring structure of bilatriene so that it can bind metal ions. In their latest work, they successfully attached rhodium and indium ions to the ring via nitrogen atoms.

The new dye showed the strongest light absorption at a wavelength of 1600 nanometers under normal conditions, which is in the second near-infrared region. It also proved to be very photostable, that is, it does not degrade when exposed to light. Detailed measurements of the molecule’s response to magnetic fields and numerical calculations using density functional theory (DFT) showed that the unique distribution of electrons in a cloud encompassing the entire complex structure of the metal-binding molecule (also known as a pi radicaloid) results in absorption that is not possible in existing, similar compounds.

Because the second near-infrared band is not as strongly absorbed by tissues, areas sensitized by the dye will be more exposed to light, allowing for clearer images and better delivery of heat for treatment. The team hopes their molecule will open the door for new approaches to deep tissue medicine as well as more general applications in chemical catalysis.

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Stepan Yuk
Medical author, Medical editor:
PhD. Olexandr Voznyak
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