New dye offers breakthrough in deep tissue imaging and cancer treatment

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

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

The effectiveness of this approach depends on the availability of stable contrast agents that can efficiently absorb light at these wavelengths. Most contrast agents, however, are most sensitive in the early near-IR region (700 – 1000 nanometers), where scattering effects are strongest 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 that overcomes this Achilles heel. Starting with a pigment from the bile pigment family called dilatriene, they applied a method known as N-confusion chemistry to modify the dilatriene ring structure to accept metal ion binding. In their most recent work, they successfully incorporated rhodium and indium ions into the ring via nitrogen atoms.

The team’s new dye showed the strongest absorption of light at a wavelength of 1600 nanometers under normal conditions, which is well within the second near-IR region. It has also been shown to be very photostable, meaning it will not easily break down when exposed to light. Detailed measurements of how the molecule responds to magnetic fields and numerical calculations using density functional theory (DFT) showed how the unique electron distribution in a cloud encompasses the entire complex structure of the metal-binding molecule (also known as a pi-radicaloid ) induced absorptions not possible in existing, similar compounds.

Since the second near-IR is not as strongly absorbed by tissues, dye-sensitized areas can be more intensely exposed to light, allowing for clearer imaging and better heat delivery for treatments. The team hopes their molecule will open the door to new approaches to deep tissue medicine, as well as more general applications in 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, Science and Technology, Sports (MEXT) under Proposal Number JPMXP1222MS1802, its Cooperative Research Program NJRC Mater. & Dev., and a Tokyo Global Partner Fellowship from Tokyo Metropolitan University.