indocyanine green

Overview

Indocyanine green (ICG) is a water-soluble tricarbocyanine dye and the only near-infrared (NIR) fluorescent agent approved by the U.S. Food and Drug Administration (FDA) for clinical use. First approved in the 1950s for hepatic function assessment, ICG absorbs and emits light in the NIR range (~700–900 nm), enabling deep-tissue optical imaging with minimal autofluorescence from biological tissues. Its strong optical properties stem from its extended conjugated cyanine backbone, which places it within the broader class of Cy5-analog dyes. ICG binds rapidly to plasma proteins — particularly human serum albumin (HSA) — following intravenous administration and is cleared almost exclusively by hepatic uptake and biliary excretion without enterohepatic recirculation, a pharmacokinetic profile that underlies its utility as both a hepatobiliary imaging agent and a surgical fluorescence guide.

Beyond its classical diagnostic role, ICG has emerged as a versatile theranostic platform. Its ability to generate reactive oxygen species (ROS) and convert absorbed photon energy into heat upon NIR irradiation makes it an effective photosensitizer and photothermal agent. These dual photodynamic and photothermal capabilities, combined with its clinical approval and relative biocompatibility, have driven extensive research into ICG-loaded nanocarriers, bioconjugates, and composite biomaterials designed to enhance tumor accumulation, extend circulation half-life, and potentiate combination cancer therapies.

Focus of Latest Publications

Recent publications on indocyanine green (ICG) have focused heavily on its use as a fluorescence-guided surgical tracer and as a component of multimodal therapeutic nanoplatforms. In breast and endometrial cancer surgery, ICG fluorescence was investigated for sentinel lymph node mapping and axillary staging, including a protocol for the INFINITE hybrid effectiveness-implementation trial aimed at evaluating real-world adoption of ICG-guided sentinel lymph node biopsy via axillary incision. A correspondence on axillary staging also highlighted methodological issues in a study of dynamic ICG lymphography drainage time, noting that the reported discrimination was derived from a narrow cohort without internal or external validation and emphasizing that clinical utility requires more than high discrimination alone.

Several studies explored ICG-based imaging and delivery systems designed to improve tumor targeting and treatment precision. In triple-negative breast cancer, tumor cell membrane-modified ICG nanoprobes were developed for near-infrared fluorescence imaging, with the coated nanoparticles showing enhanced cellular uptake, tumor accumulation, and retention of ICG’s optical and photothermal properties. Another study used biosynthetic gas vesicles conjugated with ICG to enable acoustically triggered delivery to bladder cancer xenografts, combining ultrasound, near-infrared fluorescence, and photoacoustic imaging; this approach prolonged ICG circulation, increased tumor delivery, and produced complete tumor regression after laser irradiation without detectable toxicity. A separate structure-activity study examined cyanine dyes, including ICG, in relation to hepatic uptake and excretion, reflecting continued interest in optimizing ICG’s diagnostic performance in hepatobiliary surgery.

ICG was also incorporated into photothermal, photodynamic, and combined chemo- or immunotherapeutic platforms. In colorectal cancer surgery, ICG fluorescence angiography was paired with quantitative fluorescence kinetics and machine learning to support more objective assessment of bowel perfusion and anastomotic leak risk. For cancer therapy, ICG-loaded hollow MnFe bimetallic nanoboxes were used to amplify reactive oxygen species and endoplasmic reticulum stress in lung cancer, while a thermoresponsive chitosan-based hydrogel system sustained release of ICG-containing nanocomposites to support long-term tumor immunotherapy through photothermal and ROS-mediated effects. In another immunotherapy-oriented platform, a peptide hydrogel-liposome composite enabled prolonged release of a cyclic dinucleotide and also extended release of ICG in vivo. Additional work combined ICG with copper peroxide nanoparticles to enhance photochemodynamic immunotherapy in triple-negative breast cancer by increasing singlet oxygen generation and promoting immunogenic cell death, and an infection-responsive hyaluronic acid-modified liposomal system used ICG for synergistic photothermal-photodynamic antibacterial therapy against biofilm-associated infections.