New dye offers breakthrough in deep tissue imaging and cancer therapy

Researchers from Tokyo Metropolitan University have developed a new dye that can strongly absorb second near-IR radiation and transform it to heat. Starting with a dye from the bile pigment family, they designed a unique ring structure which can bind rhodium and iridium. Measurements and modeling revealed strong second near-IR absorptions and exceptional photostability. Second near-IR waves easily penetrate human tissue; the new dye may be applied in deep tissue therapies and imaging.

The second near-IR region of the electromagnetic spectrum (1000-1700 nanometers) is a potentially important wavelength range for medical science. In this range, light is not as strongly scattered or absorbed by biological tissue. This transparency makes it ideal for delivering energy into deeper parts of the body, whether for imaging or treatments. An important example of such a therapy is photoacoustic imaging in cancer diagnosis and treatment. When a contrast agent injected into the body is hit with light, it emits heat which creates tiny ultrasonic shocks which can either be detected for imaging, or itself used to damage cancerous cells.

The efficacy of this approach hinges on the availability of stable contrast agents which can efficiently absorb light at these wavelengths. The majority of contrast agents, however, are more sensitive in the first near-IR 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 from Tokyo Metropolitan University have developed a new chemical compound which overcomes this Achilles’ heel. Starting with a dye from the bile pigment family called bilatriene, they applied a method known as N-confusion chemistry to modify the ring structure of bilatriene to accept the binding of metal ions. In their most recent work, they successfully incorporated rhodium and indium ions onto the ring via nitrogen atoms.

The team’s new dye showed its strongest light absorption at a wavelength of 1600 nanometers under normal conditions, which is well inside the second near-IR region. It was also shown to be very photostable, meaning that it won’t break apart easily on exposure to light. Detailed measurements of how the molecule responds to magnetic fields, and numerical calculations using density functional theory (DFT) both showed how the unique distribution of electrons in a cloud encompassing the whole, intricate structure of the metal-binding molecule (also known as a pi-radicaloid) gave rise to absorbances which are not possible in existing, similar compounds.

Since the second near-IR is not as strongly absorbed by tissues, regions sensitized with the dye may be exposed more strongly to light, allowing for clearer imaging and better delivery of heat for therapies. The team hopes their molecule will open the door to new approaches to deep tissue medicine, as well as more general applications to chemical catalysis.

This work was supported by JSPS Grant Numbers JP20H00406 and JP22K19937, JST PRESTO Grant Number JPMJPR2103, the Izumi Science and Technology Foundation, Advanced Research Infrastructure for Materials and Nanotechnology in Japan (ARIM) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) under proposal Number JPMXP1222MS1802, the Cooperative Research Program of NJRC Mater. & Dev., and a Tokyo Global Partner fellowship from Tokyo Metropolitan University.