KRICT develops more photostable near-infrared fluorescent dye for longer surgical imaging

Researchers in Korea have developed a new near-infrared (NIR) fluorescent dye with significantly improved photostability, overcoming the rapid signal fading that has long limited fluorescence imaging during surgery for cancer, lymph node mapping, and other medical procedures.

A research team led by Dr. Young Il Park and Dr. Sang Hwan Nam of the Korea Research Institute of Chemical Technology (KRICT, President Suk Min Shin), in collaboration with Professor Sung-Jin Park of the Georgia Institute of Technology, developed a polymerized version of the clinically approved NIR fluorescent dye indocyanine green (ICG) that exhibits greatly enhanced photostability.

Near-infrared (NIR) imaging is widely used for medical diagnosis and image-guided surgery.

Light in the near-infrared region (approximately 650–900 nm) penetrates biological tissues much more effectively than visible light because it experiences relatively low absorption by water and hemoglobin. Combined with fluorescent dyes, NIR light enables imaging of biological tissues several centimeters beneath the surface.

Currently, indocyanine green (ICG) is the only FDA-approved NIR fluorescent dye. Since receiving FDA approval in 1959, ICG has been used for more than six decades in numerous clinical applications, including sentinel lymph node mapping, liver tumor resection, and biliary tract visualization. In the United States alone, more than 750,000 laparoscopic cholecystectomies are performed annually, making ICG an indispensable surgical imaging agent.

However, ICG suffers from a major limitation: it rapidly loses fluorescence upon continuous illumination through photobleaching, reducing imaging accuracy during prolonged surgical procedures. Previous approaches attempted to encapsulate ICG inside polymeric capsules or nanostructures to improve stability, but these methods involve complex manufacturing processes and often suffer from dye leakage, limiting their clinical applicability.

The research team addressed this limitation by chemically linking ICG molecules into a polymer backbone.

Rather than protecting ICG with external carriers, the polymerization strategy stabilizes the fluorescent chromophore itself.

Normally, ICG loses fluorescence because its heptamethine chromophore reacts with oxygen generated during laser irradiation, causing irreversible structural degradation. In the newly developed fluorescent polymer, KR-NIR-P, the polymer framework partially shields the chromophore from molecular oxygen. At the same time, hydrophobic interactions within the polymer stabilize the molecular structure, allowing fluorescence to persist much longer under continuous illumination. The polymer architecture also suppresses uncontrolled molecular aggregation, another major contributor to photobleaching.

Under continuous irradiation with a 785-nm NIR laser, conventional ICG lost fluorescence rapidly, falling to approximately 40% of its initial intensity within 50 seconds. In contrast, KR-NIR-P retained approximately 66% of its initial fluorescence even after 200 seconds, representing more than a four-fold improvement in photostability.

KR-NIR-P also demonstrated excellent biocompatibility.

Cell viability remained above 90% at concentrations up to 20 μM in both cancer cells—including cervical cancer and oral squamous carcinoma cells—and normal cells. Protein analyses further showed no meaningful differences from conventional ICG in apoptosis-related biomarkers, indicating that the polymerized dye does not induce additional cellular toxicity.

The researchers further evaluated KR-NIR-P in three-dimensional tumor spheroids, which closely mimic real tumors, and confirmed that the fluorescent polymer penetrated uniformly throughout the deeper regions of the tissue.

In mouse studies, fluorescence signals appeared in the sentinel lymph node only two hours after subcutaneous injection into the footpad and became strongly accumulated after 24 hours, demonstrating the material's potential for real-time lymphatic imaging and cancer surgery.

The research team plans to further validate the safety and efficacy of KR-NIR-P through comprehensive preclinical studies, including toxicity and pharmacokinetic evaluations.

The study was published as a cover article in the June 2026 issue of Small (Impact Factor: 11.8). Dr. Young Il Park, Dr. Sang Hwan Nam, and Professor Sung-Jin Park served as corresponding authors, while Su Bin Lee, Minsuk Choi, and Young Hoon Son contributed as co-first authors.

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KRICT is a non-profit research institute funded by the Korean government. Since its foundation in 1976, KRICT has played a leading role in advancing national chemical technologies in the fields of chemistry, material science, environmental science, and chemical engineering. Now, KRICT is moving forward to become a globally leading research institute tackling the most challenging issues in the field of Chemistry and Engineering and will continue to fulfill its role in developing chemical technologies that benefit the entire world and contribute to maintaining a healthy planet. More detailed information on KRICT can be found at https://www.krict.re.kr/eng/

This research was supported by the KRICT, the Korea Basic Science Institute, and the Technology Innovation Program of the Ministry of Trade, Industry and Energy