Indocyanine Green Research Articles

A near-infrared triggered multi-functional indocyanine green nanocomposite with NO gas release function inducing improved photothermal therapy

The integration of photothermal and near-infrared (NIR) imaging capabilities of indocyanine green (ICG) small molecules has attracted considerable attention in tumor diagnosis and treatment. However, the abnormal upregulation of cellular heat shock proteins (HSPs) induced by photothermal therapy (PTT) enhances cellular heat resistance, thereby severely affecting the efficacy of PTT. In this study, to address the impact of HSPs on the efficacy of PTT while obtaining high-quality NIR fluorescence imaging in the NIR region, we designed a targeted peptide@ICG nanofluorescent probe encapsulated in liposomes. The introduced cRGD targeting peptide not only possesses tumor-targeting capabilities but also features LA as the last amino acid in the targeting peptide, which can generate nitric oxide (NO) under reactive oxygen species (ROS) triggering. It can happen under 808 nm single-light source NIR light, and the guanidine group in the peptide decomposes and combines with singlet oxygen molecules to generate NO gas molecules, thereby exerting an elevated photothermal effect by inhibiting the expression of HSP70. In addition, the nanoprobes enable deep imaging and treatment of glioma in situ and can be combined with a laser speckle contrast imaging (LSCI) system for multimodal imaging. This composite probe demonstrates synergistic tumor therapeutic effects of photodynamic therapy (PDT), PTT, and gas therapy, offering a promising strategy for cancer treatment.

Melatonin enhances therapeutic outcomes of adipose tissue-derived mesenchymal stem cell therapy in rat osteoarthritis by reducing TNF-α and IL-1β-induced injuries.

Although adipose tissue-derived mesenchymal stem cell (ADSC) transplantation has been effectively used to treat osteoarthritis (OA), the low cell survival rate induced by the inflammatory and oxidative stress, severely affects the therapeutic efficiency of ADSC transplantation in OA. This study was designed to evaluate whether melatonin pretreatment could improve ADSC survival and its therapeutic efficacy in OA. The papain-induced OA rats were pretreated with melatonin via intra-articular injection and then intra-articular injected with indocyanine green (ICG)-labeled ADSCs (3 × 106/rat). Afterward, ADSC retention was evaluated by NIR-II fluorescence imaging. The tibia and synovial fluid were collected for histopathological examination and ELISA assay, respectively. To confirm the anti-inflammatory effect of melatonin, a TNF-α and IL-1β-induced cell model was used to evaluate the protective effects of melatonin on ADSC viability, cell apoptosis, and migration. Our results showed that melatonin pretreatment enhanced ADSC survival and improved the therapeutic effects of ADSC transplantation on cartilage repair, and anti-inflammation by reducing TNF-α, IL-6, IL-1β, and IL-12 in vivo. In particular, we also found that melatonin promoted ADSC viability and migration, and reduced cell apoptosis in vitro. In conclusion, this study supports that melatonin pretreatment can effectively improve ADSC survival and therapeutic efficiency in OA by reducing inflammatory injuries, which provides a novel strategy for enhancing ADSC therapy.

Lymphatic Fistula Treatment: Indocyanine Green Lymphography-guided Microsurgery

Background: Lymphatic fistulas are a common complication from surgery or interventional procedures resulting in persistent lymphatic leakage and delayed wound healing. The management of lymphatic fistula remains a subject of debate, ranging from conservative treatment to surgical lymphatic ligation. The implementation of a novel microsurgical approach involving lymphatic fistula ligation and/or lymphovenous anastomosis (LVA) using indocyanine green (ICG) lymphography is expected to decrease occurrence and complications. In this study, we share our experience in treating lymphatic fistula–guided microsurgical treatment. Methods: A total of 13 patients from our hospital with persistent lymphatic fistula were enrolled in this retrospective study. Lymphatic fistulas and their leakages were identified and ligated by using ICG lymphography and a surgical microscope. In two cases, additional LVA surgery was performed. Results: We were able to precisely identify lymphatic fistulas and treat them in all 13 patients. Lymph ligation was performed in all 13 cases, with additional distal LVA in two cases. In all patients, wound healing occurred following lymphatic ligation, except in one patient due to persistent infection. Patients with a lymphatic fistula were referred to our unit within 3 weeks to 1 year after onset, with an average consultation occurring after 5 months of persistent lymphatic fistula. Conclusions: Targeted lymphatic vessel ligation with or without LVA with ICG-guided surgical microscope represents a promising highly efficacious therapy for persistent lymphatic fistula. This technique may accelerate wound healing and reduce hospitalization duration, thus advocating for its preferential use in managing lymphatic fistulas.

Platelet membrane-coated oncolytic vaccinia virus with indocyanine green for the second near-infrared imaging guided multi-modal therapy of colorectal cancer

Colorectal cancer (CRC) is a prevalent malignancy with insidious onset and diagnostic challenges, highlighting the need for therapeutic approaches to enhance theranostic outcomes. In this study, we elucidated the unique temperature-resistant properties of the oncolytic vaccinia virus (OVV), which can synergistically target tumors under photothermal conditions. To capitalize on this characteristic, we harnessed the potential of the OVV by surface-loading it with indocyanine green (ICG) and encapsulating it within a platelet membrane (PLTM), resulting in the creation of PLTM-ICG-OVV (PIOVV). This complex seamlessly integrates virotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT). The morphology, size, dispersion stability, optical properties, and cellular uptake of PIOVV were evaluated using transmission electron microscopy (TEM). In vitro and in vivo experiments revealed specificity of PIOVV for cancer cells; it effectively induced apoptosis and suppressed CT26 cell proliferation. In mouse models, PIOVV exhibits enhanced fluorescence at tumor sites, accompanied by prolonged blood circulation. Under 808 nm laser irradiation, PIOVV significantly inhibited tumor growth. This strategy holds the potential for advancing phototherapy, oncolytic virology, drug delivery, and tumor-specific targeting, particularly in the context of CRC theranostics.

The“Overlapping”Lymphaticovenous Anastomosis: an overlapped end-to-end anastomosis supermicrosurgical technique

ObjectiveLymphaticovenular anastomosis (LVA) is increasingly utilized in the treatment of lymphedema. This study aims to assess the efficacy and safety of the “Overlapping” LVA technique, which addresses the size mismatch between lymphatic and venous vessels in lymphedema treatment.MethodsBetween August 2022 and April 2023, seventeen patients diagnosed with lymphedema were enrolled in this study. The severity of lymphedema in these patients was classified according to the International Society of Lymphology (ISL) staging system.All patient underwent LVA procedures, anastomosis techniques including the Overlapping, end-to-end and octopus anastomosis. The techniques of anastomosis, anastomosis time, patency rate, and volume of limb lymphedema were evaluated.ResultsOur study enrolled 17 lymphedema patients who underwent the LVA procedure. All patients showed significant postoperative improvement in limb edema. The mean drainage volume was 472.29 ml. The Overlapping technique demonstrated a 100% success rate as assessed by clinical observation and intraoperative Indocyanine Green (ICG) lymphography. The average anastomosis time was 5.3 min, reducing operative time compared to traditional methods.ConclusionsThese findings suggest that the Overlapping technique could serve as a valuable addition to the current LVA technique. This Overlapping anastomosis technique provides a wide range of applications for lymphatic anastomosis treatment and prevention of lymphedema.

Navigating Lymphedema: The Impact of Indocyanine Green Lymphography on Personalized Therapy Outcomes in Breast Cancer Patients

AimTo evaluate the role of Indocyanine Green Lymphography (ICG_L) in the early diagnosis and personalized management of breast cancer-related lymphedema (BCRL) among high-risk breast cancer (BC) survivors. MethodsPatients who admitted to the UPMC Magee-Womens Hospital Lymphedema Program between October 2018 and December 2021 with episodic symptoms were enrolled into the study. Patient demographics, clinical characteristics, and outcomes were prospectively collected and retrospectively analysed. Lymphatic flow disruptions were identified and guided personalized therapeutic interventions were guided by ICG_L. ResultsAmong 154 BC survivors, 184 arms were evaluated. Initial ICG_L showed 57.1% had no lymphedema, while 42.9% were classified as stage 1 to 3 lymphedema. Early diagnosis and personalized interventions provided improved outcomes, with only 4.3% developing clinical lymphedema after a median follow-up of 27 months. Patients exhibited stable or improved symptoms with individualized treatments such as manual lymphatic drainage, compression therapies, and physiotherapy. ConclusionICG_L evaluation is essential for patients at high-risk of developing BCRL. Early diagnosis before clinical onset of lymphedema, and ICG_L guided therapy significantly enhances the clinical outcomes and improves lymphedema management. Micro AbstractBreast cancer-related lymphedema (BCRL) is a common complication following breast cancer treatment, characterized by chronic swelling and functional impairment. This study investigates the role of indocyanine green lymphography (ICG_L) for early BCRL detection among high-risk breast cancer survivors. By identifying subclinical lymphatic disruptions, personalized physical therapy interventions are implemented, leading to improved patient outcomes. With a median follow-up of 27 months, only 4.3% of patients developed clinical BCRL, highlighting the efficacy of early diagnosis and tailored preventive strategies in managing lymphedema progression.

MA03.05 Intraoperative Visualization of Pulmonary Nodules with Indocyanine Green Inhalation Under Near-Infrared Window I and II

MA03.05 Intraoperative Visualization of Pulmonary Nodules with Indocyanine Green Inhalation Under Near-Infrared Window I and II

EP.07A.20 Intraoperative Near-infrared Fluorescence Visualization of the Pulmonary Bronchus with Indocyanine Green Inhalation

EP.07A.20 Intraoperative Near-infrared Fluorescence Visualization of the Pulmonary Bronchus with Indocyanine Green Inhalation

Excessive autophagy-inducing and highly penetrable biomineralized bacteria for multimodal imaging-guided and mild hyperthermia-enhanced immunogenic cell death

The tumor microenvironment, characterized by hypoxia, supports the efficacy of anaerobic bacteria like attenuated S. typhimurium in cancer therapies. These bacteria target and penetrate deep tumor regions, significantly reducing tumor size but often lead to tumor regrowth due to limited long-term efficacy. To enhance the therapeutic impact, a novel biohybrid system, S@UIL, has been developed by coating S. typhimurium with a zirconium-based nanoscale metal–organic framework (UiO-66-NH2) loaded with indocyanine green (ICG) and luteolin (LUT). This system maintains the bacteria’s tumor-targeting ability while increasing the penetration and therapeutic effectiveness through excessive autophagy and mild hyperthermia. In a subcutaneous colon cancer model, the integration of LUT and ICG promotes autophagic cell death and photothermal sensitization, leading to the release of damage-associated molecular patterns (DAMPs). These DAMPs activate immune responses through dendritic cells and T-cells, enhancing immunogenic cell death (ICD) and potentially reducing immune evasion by tumors. This single-administration approach also integrates multimodal imaging capabilities, providing a promising strategy for improved tumor ICD induction and cancer progression inhibition.

A New Vision in Endometriosis Surgery: The Impact of Near-Infrared Indocyanine Green Fluorescence Imaging

A New Vision in Endometriosis Surgery: The Impact of Near-Infrared Indocyanine Green Fluorescence Imaging

Use of indocyanine green-human serum albumin complexes in fluorescence image-guided laparoscopic anatomical liver resection: a case series study (with video)

BackgroundThis study aimed to investigate the feasibility and efficacy of near-infrared fluorescence-guided laparoscopic anatomical hepatectomy (LAH) using a novel indocyanine green (ICG)-human serum albumin complex (HSA) in patients with hepatocellular carcinoma.MethodsClinical data of hepatocellular carcinoma patients who underwent ICG-HSA fluorescence-guided LAH at our center from January 2024 to April 2024 were prospectively collected and analyzed. Ultraviolet absorption spectroscopy was used to test the absorption and stability of ICG-HSA complex solutions under different conditions. After determining the optimal ratio, the complex was administered intravenously during surgery to perform negative staining via Glissonean pedicle isolation. LAH was performed along the fluorescence-demarcated boundaries.ResultsThirty-one patients were included (24 men; mean age, 54.61 ± 13.54 years). The median maximum tumor diameter was 2.80 (interquartile range [IQR], 2.00–4.00) cm. S8 segmentectomy (22.6%) and right posterior segmentectomy (19.4%) were the most common resections performed. Successful fluorescence negative staining was achieved in all patients using ICG and HSA at a 1:6 molar ratio at room temperature. Mean operation time was 297.58 ± 85.53 min, Median intraoperative blood loss was 100.0 mL (IQR, 50.0–200.0). The median surgical margin distance was 0.90 cm (IQR, 0.40–1.50). The postoperative complication rate was 45.2% (35.5% Clavien–Dindo grade I and 9.7% grade II). The median length of hospital stay was 5.0 days (IQR, 4.0–5.0).ConclusionICG-HSA-assisted LAH is safe and feasible. Compared with free ICG, the novel ICG-HSA complex exhibits better optical properties and in vivo stability, which can improve the accuracy of intraoperative liver segment localization and optimize the anatomical dissection plane. It has the potential to become an ideal fluorescent imaging agent for anatomical hepatectomy.Graphical abstractA In vitro binding experiments of indocyanine green (ICG) and human serum albumin (HSA) suggested that a 1:6 molar ratio and a configuration temperature of 37°C were optimal. B During surgery, after extrahepatic Glissonean isolation of the liver pedicle planned for resection, the ICG-HSA complex was administered through a peripheral vein using an infusion pump. C ICG-HSA metabolism comprises three stages: intravascular, liver, and systemic clearance. D The actual intraoperative fluorescence imaging and guidance effects of ICG-HSA in laparoscopic fluorescence negative-staining right hemihepatectomy.

Emissive Lipid Nanoparticles as Biophotonic Contrast Agent for Site-Selective Solid Tumor Imaging in Pre-Clinical Models.

Small organic dye-based fluorescent agents are highly potent in solid tumor imaging but face challenges such as poor photostability, nonspecific distribution, low circulation, and weak tumor binding. Nanocarriers overcome these issues with better physicochemical and biological performance, particularly in cancer imaging. Among the various nanosized carriers, lipid formulations are clinically approved but yet to be designed as bright nanocontrast agents for solid tumor diagnosis without affecting surrounding tissues. Herein, indocyanine green (ICG) encapsulated targetable lipid nanoparticles (698 ICG/LNPs) as safe contrast agents (∼200 nm) have been developed and tested for solid tumor imaging and biodistribution. Our findings reveal that nanoprecipitation produces ICG-LNPs with a unique assembly, which contributes to their high brightness with improved quantum yield (3.5%) in aqueous media. The bright, optically stable (30 days) biophotonic agents demonstrate rapid accumulation (within 1 h) and prolonged retention (for up to 168 h) at the primary tumor site, with better signal intensity following a one-time dose administration (17.7 × 109 LNP per dose). Incorporated folic acid (735 folic acid/LNPs) helps in selective tumor binding and the specific biodistribution of intravenously injected nanoparticles without affecting healthy tissues. Designed targetable ICG-LNP (634 MESF) demonstrates high-contrast fluorescence and resolution from the tumor area as compared to the targetable ICG-liposomal nanoparticles (532 MESF). Various in vitro and in vivo findings reveal that the cancer diagnostic efficacy elicited by designed bright lipid nanoparticles are comparable to reported clinically accepted imaging agents. Thus, such LNPs hold translational potential for cancer diagnosis at an early stage.

Optimizing the technical results of robotic esophagectomy: conduit creation and esophagogastric anastomoses

The esophagectomy, first done over a century ago, has evolved from open procedures to minimally invasive techniques. As minimally invasive surgery has progressed in both safety and efficiency since its inception, it is becoming increasingly favored and continues to demonstrate advantageous outcomes over open techniques. In terms of operative decisions, conduit diameter choice is crucial in esophagectomy. Narrower conduits (≤ 3 cm) seem to be more efficacious, and less prone to stricture than their wider counterparts (> 5 cm). Perfusion assessment, notably with indocyanine green (ICG), is still a topic of debate among surgeons with conflicting opinions on ICG’s impact. There are varying results in leak rates; however, the use of ICG in determining anastomotic site seems to exert some influence on surgical decision-making. Anastomotic techniques, such as circular stapling and linear stapling, have shown to be preferred over more traditional hand-sewn methods. At our institution, a completely robotic approach is used with creation of a 3-4 cm wide conduit and hybrid-type anastomosis. ICG is used to guide conduit transection and gastrotomy for anastomosis. Our experience shows that this approach offers an excellent combination of safety and reproducibility.

MnO2 nanozyme boosts synergistic photodynamic/photothermal therapy of bacterial biofilm infections

As a near-infrared (NIR) adsorbing dye approved by the FDA, indocyanine green (ICG) can serve as an attractive therapeutic agent to combat biofilm infections through synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) due to its deep-tissue penetration ability. However, ICG usually suffers from photo/thermal instability. Herein, to tackle the issues, bovine serum albumin (BSA) stabilized nanozyme MnO2 (BSA/MnO2) was synthesized by reducing manganese permanganate (KMnO4) with BSA, which was further loaded with ICG and coated with the positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as the bacterial targeting moiety through noncovalent interactions. The constructed ICG@BSA/MnO2@HACC (IBMH) displays good photodynamic/thermal effects and bacterial targetability, enabling a synergistic PDT/PTT therapy against biofilm-associated infections. Compared with free ICG, IBMH exhibits enhanced photo/thermal stability owing to the O2-generating and photothermal capacities of MnO2, which significantly promotes biofilm phototherapy. Meanwhile, IBMH can effectively achieve anti-inflammatory effect due to the reactive oxygen species (ROS) scavenging capacity of nanozyme MnO2, thereby greatly accelerating wound healing after synergistic PDT/PTT. Both in vitro and in vivo assays solidly demonstrate its satisfactory anti-biofilm and anti-inflammatory effects. Therefore, our research proposes a promising and convenient strategy for developing multifunctional nanozyme for synergistic PDT/PTT of biofilm infection.

Peroxidase-Mimetic Iron Silicate Nanosheets Coordinated with Indocyanine Green for Enhanced Anti-Tumor Therapy.

The versatile element composition and multifunctional properties of biodegradable silicates have attracted significant attention in cancer therapeutics. However, their application as nanozymes is often limited by suboptimal catalytic efficiency and insufficient intratumoral retention. In this study, the hydrothermal synthesis of iron silicate (FeSi) nanosheets are reported exhibiting exceptional peroxidase (POD)-like activity (136.7Umg-1), outperforming most reported iron-based nanozymes. Density functional theory calculations revealed that the introduction of Si into the catalyst enhances H2O2 adsorption and dissociation of Fe sites, leading to superior POD performance. Furthermore, the FeSi nanosheets are modified with Indocyanine Green (ICG) to facilitate targeted aggregation-potentiated therapy. The integration of ICG improved tumor penetration and retention of the FeSi nanosheets, significantly increasing their reactive oxygen species production and bolstering therapeutic efficacy.

A near-infrared fluorescent probe with assembly/aggregation-induced retention effect for specific diagnosis of metastasis and image-guided surgery in breast cancer

Image-guided surgery is crucial for achieving complete tumor resection, reducing postoperative recurrence and improving patient survival. However, current clinical near-infrared fluorescent probes, such as indocyanine green (ICG), face two main limitations: 1) lack of active tumor targeting, and 2) short retention time in tumors, which restricts real-time imaging during surgery. To address these issues, we developed a near-infrared fluorescent probe capable of in situ nanofiber formation within tumor lesions. This probe actively targets the integrin αvβ3 receptors overexpressed on breast cancer cells and exhibits assembly/aggregation-induced retention effects at the tumor site, significantly extending the imaging time window. Additionally, we found that the probe's fluorescence intensity can be enhanced under receptor induction. Due to its excellent tumor specificity and sensitivity, 1FCG-FFGRGD not only identifies primary breast cancer but also precisely locates smaller lymph node metastases and detects sub-millimeter peritoneal metastases. In summary, this near-infrared probe, leveraging assembly/aggregation-induced retention effects, holds substantial potential for various biomedical applications.

The use of indocyanine green for colorectal anastomoses: a systematic review and meta-analysis.

Anastomotic leak is a relatively common and debilitating complication. Colorectal leak rates vary widely in the literature, ranging from 1% to 20%. In modern surgical practice, there is much emphasis on the use of indocyanine green (ICG). This is a fluorescent dye administered intravenously to locate and predict an adequate line of anastomosis. We sought to analyse the current literature and supporting evidence behind the use of ICG in the context of elective colorectal surgery. A literature search was conducted for papers published between January 1991 and December 2022 concerning the use of ICG in colorectal surgery. Data on anastomotic leak, overall complication rate, operative time and involvement of artificial intelligence (AI) were compared. A total of 24 studies were selected, including 3 randomised controlled trials. There was an anastomotic leak rate of 4.3% in cases with ICG administration compared with 9.5% in the control group (p<0.00001). Seven studies mentioned overall complication rates. These were lower in the ICG cohort than in the control group (15.5% vs 24.5%). There was no significant correlation between ICG use and operative time (p=0.78). Five studies looked at AI, with results suggesting that use of AI leads to much better accuracy in ICG metric analysis. However, the current literature is still inconclusive. While there is strong evidence behind ICG use in the existing literature, more randomised controlled trials are required for better recommendations. AI in ICG metric interpretation has proved to be difficult owing to interpatient variability. Nevertheless, new data suggest better understanding and standardisation.

Diagnosis of Lymphedema and Subjective Symptoms in the Lower Abdomen and Genital Region.

Background: Lymphedema in the lower abdomen and genitals is unnoticeable and has no established diagnostic methods. In this study, we evaluated it using four examinations. Methods: We evaluated 25 patients with lymphedema in the legs, dividing the abdomen and genitals in four areas (right and left, upper and lower). The mean age was 58.6 years. In lymphoscintigraphy and indocyanine green (ICG) lymphography, we diagnosed lymphedema when dermal backflow was observed. ICG lymphography was performed in 13 patients. In ultrasonography, we determined the presence of edema when cobblestone pattern was observed. Subcutaneous fat thickness was also measured. The patients' subjective symptoms were identified on an interview. We compared the results among the examinations. Results: The positivity rates for lymphedema based on lymphoscintigraphy, ICG lymphography, ultrasonography, and subjective symptoms were 45.0%, 42.3%, 8.0%, and 34.0%, respectively. Two of the 13 patients who underwent all examinations complained of subjective symptoms of edema in areas that showed no abnormalities in the examinations. In contrast, 14 of the 25 patients had areas where they had no subjective symptoms despite having abnormalities in at least one of the tests. Those with subjective symptoms of edema tended to have thinner abdominal fat in both the upper and lower abdomen, but no significant difference was observed. Conclusion: Large differences were observed in the positive rate of edema in subjective symptoms and examinations of lymphedema in the lower abdomen and genitals. It is not important to determine which examination is best but rather to combine multiple examinations.

A Novel Method of Management of High Output Chyle Leak Following Neck Dissection: Indocyanine Green Fluorescence-guided Robotic Transthoracic Thoracic Duct Ligation: A Case Series

A Novel Method of Management of High Output Chyle Leak Following Neck Dissection: Indocyanine Green Fluorescence-guided Robotic Transthoracic Thoracic Duct Ligation: A Case Series

Spatiotemporal Delivery of Dual Nanobodies by Engineered Probiotics to Reverse Tumor Immunosuppression via Targeting Tumor-Derived Exosomes.

The anti-PD-L1 and its bispecific antibodies have exhibited durable antitumor immunity but still elicit immunosuppression mainly caused by tumor-derived exosomes (TDEs), leading to difficulty in clinical transformation. Herein, engineered Escherichia coli Nissle 1917 (EcN) coexpressing anti-PD-L1 and anti-CD9 nanobodies (EcN-Nb) are developed and decorated with zinc-based metal-organic frameworks (MOFs) loaded with indocyanine green (ICG), to generate EcN-Nb-ZIF-8CHO-ICG (ENZC) for spatiotemporal lysis of bacteria for immunotherapy. The tumor-homing hybrid system can specifically release nanobodies in response to near-infrared (NIR) radiation, thereby targeting TDEs and changing their biological distribution, remodeling tumor-associated macrophages to M1 states, activating more effective and cytotoxic T lymphocytes, and finally, leading to the inhibition of tumor proliferation and metastasis. Altogether, the microfluidic-enabled MOF-modified engineered probiotics target TDEs and activate the antitumor immune response in a spatiotemporally manipulated manner, offering promising TDE-targeted immune therapy.