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.

Key Publications

• NEWJun Discrimination, spectrum, and clinical utility: ICG lymphography drainage time in axillary staging. (Breast cancer research and treatment, 2026, PMID 42360511): "...dynamic indocyanine green (ICG) lymphography drainage time as a marker of axillary nodal burden."
• NEWJun Fluorescence imaging using indocyanine green to identify sentinel lymph nodes during surgery for breast cancer (INFINITE): protocol for a hybrid effectiveness-implementation trial using a stepped-wedge cluster design. (BMJ open, 2026, PMID 42342397): "Indocyanine green (ICG) fluorescence is a non-radioactive alternative, offering real-time visualisation while addressing many limitations of traditional tracers."
• May Interpretable and non-linear machine learning models for quantitative ICG perfusion assessment in colorectal cancer anastomosis: A feasibility study. (European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2026, PMID 42202707): "Intraoperative indocyanine green (ICG) fluorescence angiography is widely used to assess bowel perfusion, but interpretation is largely subjective."
• May Sentinel Lymph Node Mapping with Indocyanine Green in Endometrial Cancer: Does the Minimally Invasive Platform Matter? (Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2026, PMID 42157366): "To compare indocyanine green (ICG) sentinel lymph node (SLN) mapping between conventional laparoscopy and robot-assisted surgery in apparent early-stage endometrial cancer."
• May Acoustic delivery of indocyanine green via biosynthetic gas vesicles for tumor photothermal therapy. (PLoS biology, 2026, PMID 42127030): "Indocyanine green (ICG) is the only U.S. Food and Drug Administration (FDA)-approved photothermal agent."
• Apr Hyaluronic acid-engineered infection-responsive liposomes achieve biofilm penetration and synergistic photothermal-photodynamic antibacterial therapy. (Carbohydrate polymers, 2026, PMID 42067348): "Upon near-infrared irradiation, indocyanine green (ICG) generates reactive oxygen species and localized heat, inducing bacterial membrane disruption and biofilm disintegration."
• May Tumor cell membrane modified clinical lCG nanoprobes for NIR fluorescence imaging of targeted triple negative breast cancer. (Biomedical materials (Bristol, England), 2026, PMID 42049061): "In this study, fluorescent dye-clinical indocyanine green (ICG) was successfully encapsulated by TNBC cell membranes via dual biolayer method to form M-ICG NPs."
• May Hollow MnFe Bimetallic Nanoboxes for Photo/Chemodynamic Therapy via Amplification of Endoplasmic Reticulum Stress. (ACS applied materials & interfaces, 2026, PMID 42044265): "Herein, we synthesized Mn/Fe bimetallic Prussian blue analog (PBA) nanoboxes (BMNs) via a facile sodium citrate-assisted method that enables template-free formation of hollow structures, which were loaded with indocyanine green (ICG) to form BMN@ICG for lung cancer treatment."
• Apr Structure-Activity Relationship of Cyanine Dyes in Relation to the Hepatic Uptake and Excretion. (Chembiochem : a European journal of chemical biology, 2026, PMID 41996556): "Indocyanine green (ICG) is a clinically approved fluorescent dye that is used for lesion identification during hepatobiliary surgery."
• May Thermoresponsive Chitosan Nanocomposite-Based Double-Network Hydrogel for Sustained Tumor Immunotherapy. (Biomacromolecules, 2026, PMID 41842712): "The system integrated indocyanine green (ICG)-loaded gold nanorods within boronic acid-modified mesoporous silica (GSB) and thermoresponsive nanocomposites (ICG@GAN), which were further loaded with β-glycerophosphate (β-GP) and genipin and embedded in a carboxymethyl chitosan matrix."