Search Results (53)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Introduction: Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) is now widely regarded as a valuable aid in decision-making for complex hepatobiliary procedures, with increasing support from recent studies. Methods: We performed a systematic review following PRISMA guidelines, utilizing PubMed, CINAHL, and EMBASE databases to locate studies on the perioperative use ICG in pediatric hepatobiliary surgeries. Two independent reviewers assessed all articles for eligibility based on predefined inclusion criteria. We collected data on study design, patient demographics, surgical indications, ICG dosing, timing of ICG injection, and perioperative outcomes. Results: Forty-three articles, including 930 pediatric patients, from 1989 to 2025 met the inclusion criteria for narrative synthesis in our systematic review, of which 22/43 (51.2%) were retrospective studies, 15/43 were case reports (34.9%), 3/43 (7.0%) were experimental studies, and the other three were prospective comparative studies (7.0%). The current clinical applications of ICG in hepatobiliary pediatric surgery include bile duct surgery (cholecystectomy, choledochal cyst, biliary atresia), reported in 17 articles (39.5%), liver tumor resection, reported in 15 articles (34.9%), liver transplantation, reported in 6 articles (14.6%), and liver function determination, reported in 5 articles (12.2%). Conclusions: ICG fluorescence navigation in pediatric hepatobiliary surgery is a highly promising and safe technology that allows for the intraoperative localization of anatomic biliary structures, aids in the identification and resection of liver tumors, and can accurately determine hepatic function. The lack of comparative and prospective studies, and the variability of the dose and timing of administration are the main limitations. Full article

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction ¹⁰B (n, alpha) ⁷Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome^® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either ¹⁰B-Carb or ¹⁰B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any ¹⁰B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with ¹⁰B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”. Full article

In this study, we aimed to demonstrate the feasibility and safety of navigating the ureters, middle sacral artery (MSA), and superior hypogastric nerve (SHN) using indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during robot-assisted sacrocolpopexy (RSCP). Overall, 15 patients who underwent RSCP for apical vaginal prolapse were retrospectively enrolled. All patients underwent cystoscopic intraureteric instillation of 5 cc ICG (2.5 mg/mL) before RSCP and intravenous injection of 3 cc ICG during presacral dissection and mesh fixation. In all patients, the fluorescent right ureter was clearly identified in real time. The MSA was visualized on ICG-NIRF images in 80% (13/15) of patients. The mean time from ICG injection to MSA visualization was 43.7 s; the mean duration of the arterial phase was 104.3 s. Fluorescent SHN was detected in 73.3% (11/15) of patients. The time from ICG injection to SHN fluorescence was 48.4 s; the duration of fluorescence was 177.2 s. There was no transfusion, iatrogenic ureteral injury, or bowel or urinary dysfunction. Our results indicated that intraoperative ureter, MSA, and SHN mapping using ICG-NIRF images during RSCP is a valuable and safe technique to avoid iatrogenic ureteral, vascular, and neural injuries and to simplify surgical procedures. Nonetheless, further studies are required. Full article

We developed a novel site-specific bimodal MRI/fluorescence nanoparticle contrast agent targeting gastrin-releasing peptide receptors (GRPrs), which are overexpressed in aggressive prostate cancers. Biocompatible ultra-small superparamagnetic iron oxide (USPIO) nanoparticles were synthesized using glucose and casein coatings, followed by conjugation with a Cy7.5-K-8AOC-BBN [7-14] peptide conjugate. The resulting USPIO(Cy7.5)-BBN nanoparticles were purified by 100 kDa membrane dialysis and fully characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and magnetic resonance imaging (MRI) relaxivity, as well as evaluated for in vitro and in vivo binding specificity and imaging efficacy in PC-3 prostate cancer cells and xenografted tumor-bearing mice. The USPIO(Cy7.5)-BBN nanoparticles had a core diameter of 4.93 ± 0.31 nm and a hydrodynamic diameter of 35.56 ± 0.58 nm. The r₂ relaxivity was measured to be 70.2 ± 2.5 s⁻¹ mM⁻¹ at 7T MRI. The Cy7.5-K-8AOC-BBN [7-14] peptide-to-nanoparticle ratio was determined to be 21:1. The in vitro GRPr inhibitory binding (IC₅₀) value was 2.5 ± 0.7 nM, indicating a very high binding affinity of USPIO(Cy7.5)-BBN to the GRPr on PC-3 cells. In vivo MRI showed significant tumor-to-muscle contrast enhancement in the uptake group at 4 h (31.1 ± 3.4%) and 24 h (25.7 ± 2.1%) post-injection compared to the blocking group (4 h: 15.3 ± 2.0% and 24 h: −2.8 ± 6.8%; p < 0.005). In vivo and ex vivo near-infrared fluorescence (NIRF) imaging revealed significantly increased fluorescence in tumors in the uptake group compared to the blocking group. These findings demonstrate the high specificity of bimodal USPIO(Cy7.5)-BBN nanoparticles towards GRPr-expressing PC-3 cells, suggesting their potential for targeted imaging in aggressive prostate cancer. Full article

Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) are gaining traction in tumor theranostics for their effectiveness in encapsulating both imaging agents and therapeutic drugs. While typically, similar hydrophilic molecules are encapsulated in either pure aqueous or organic environments, few studies have explored co-encapsulation of chemotherapeutic drugs and imaging agents with varying hydrophilicity and, consequently, constructed multifunctional ZIF-8 composite NPs for acid-responsive, near-infrared fluorescence imaging/chemotherapy combined tumor theranostics. Here, we present a one-pot method for the synthesis of uniform Cy5.5&DOX@ZIF-8 nanoparticles in mixed solvents, efficiently achieving simultaneous encapsulation of hydrophilic doxorubicin (DOX) and hydrophobic Cyanine-5.5 (Cy5.5). Surface decoration with dextran (Dex) enhanced colloidal stability and biocompatibility. The method significantly facilitated co-loading of Cy5.5 dyes and DOX drugs, endowing the composite NPs with notable fluorescent imaging capabilities and pH-responsive chemotherapy capacities. In vivo near-infrared fluorescence (NIRF) imaging in A549 tumor-bearing mice demonstrated significant accumulation of Cy5.5 at tumor sites due to enhanced permeability and retention (EPR) effects, with fluorescence intensities approximately 48-fold higher than free Cy5.5. Enhanced therapeutic efficiency was observed in composite NPs compared to free DOX, validating tumor-targeted capability. These findings suggest ZIF-8-based nanomedicines as promising platforms for multifunctional tumor theranostics. Full article

Background: Indocyanine green (ICG) near-infrared fluorescence (NIRF) has emerged as a promising technique for visualizing tissue perfusion. However, within the wide range of dosages and imaging conditions currently being applied, the optimal dosage of ICG remains unclear. This study aimed to investigate the feasibility and implications of implementing lower dosages of ICG than commonly used for visual and quantitative perfusion assessment in a standardized setting. Methods: A prospective single-center cohort study was conducted on patients undergoing ileostomy reversal by hand-sewn anastomosis. ICG-NIRF visualization was performed before (T1) and after (T2) anastomosis with one of four different dosages of ICG (5 mg, 2.5 mg, 1.25 mg, or 0.625 mg) and recorded. Postoperatively, each visualization was evaluated for signal strength, completeness, and homogeneity of fluorescence. Additionally, perfusion graphs were generated by a software-based quantitative perfusion assessment, allowing an analysis of perfusion parameters. Statistical analysis comparing the effect of the investigated dosages on these parameters was performed. Results: In total, 40 patients were investigated. Visual evaluation demonstrated strong, complete, and homogeneous fluorescence signals across all dosages. Perfusion graph assessment revealed a consistent shape for all dosages (ingress followed by egress phase). While the average signal intensity decreased with dosage, it was sufficient to enable perfusion assessment even at the lowest dosages of 1.25 mg and 0.625 mg of ICG. The baseline intensity at T2 (the second intraoperative visualization) significantly decreased with dosage. The slope of the egress phase steepened with decreasing dosage. Conclusions: Lower dosages of ICG were sufficient for intraoperative perfusion assessment, while causing lower residual fluorescence and quicker egress in subsequent visualizations. Full article

Lymphedema is a progressive condition. Its therapy aims to reduce edema, prevent its progression, and provide psychosocial aid. Nonsurgical treatment in advanced stages is mostly insufficient. Therefore—in many cases—surgical procedures, such as to restore lymph flow or excise lymphedema tissues, are the only ways to improve patients’ quality of life. Imaging modalities: Lymphoscintigraphy (LS), near-infrared fluorescent (NIRF) imaging—also termed indocyanine green (ICG) lymphography (ICG-L)—ultrasonography (US), magnetic resonance lymphangiography (MRL), computed tomography (CT), photoacoustic imaging (PAI), and optical coherence tomography (OCT) are standardized techniques, which can be utilized in lymphedema diagnosis, staging, treatment, and follow-up. Conclusions: The combined use of these imaging modalities and self-assessment questionnaires deliver objective parameters for choosing the most suitable surgical therapy and achieving the best possible postoperative outcome. Full article

Assessment of regional lymph node status in breast cancer is of important staging and prognostic value. Even though formal histological examination is the currently accepted standard of care, optical imaging techniques have shown promising results in disease diagnosis. In the present article, we review six spectroscopic techniques and focus on their use as alternative tools for breast cancer lymph node assessment. Elastic scattering spectroscopy (ESS) seems to offer a simple, cost-effective, and reproducible method for intraoperative diagnosis of breast cancer lymph node metastasis. Optical coherence tomography (OCT) provides high-resolution tissue scanning, along with a short data acquisition time. However, it is relatively costly and experimentally complex. Raman spectroscopy proves to be a highly accurate method for the identification of malignant axillary lymph nodes, and it has been further validated in the setting of head and neck cancers. Still, it remains time-consuming. Near-infrared fluorescence imaging (NIRF) and diffuse reflectance spectroscopy (DFS) are related to significant advantages, such as deep tissue penetration and efficiency. Fourier-transform infrared spectroscopy (FTIR) is a promising method but has significant drawbacks. Nonetheless, only anecdotal reports exist on their clinical use for cancerous lymph node detection. Our results indicate that optical imaging methods can create informative and rapid tools to effectively guide surgical decision-making. Full article

We recently developed a novel hyperspectral excitation-resolved near-infrared fluorescence imaging system (HER-NIRF) based on a continuous-wave wavelength-swept laser. In this study, this technique is applied to measure the distribution of the therapeutic agent dimethyl sulfoxide (DMSO) by utilizing solvatochromic shift in the spectral profile of albumin-bound Indocyanine green (ICG). Using wide-field imaging in turbid media, complex dynamics of albumin-bound ICG are measured in mixtures of dimethyl sulfoxide (DMSO) and water. Phantom experiments are conducted to evaluate the performance of the HER-NIRF system. The results show that the distribution of DMSO can be visualized in the wide-field reflection geometry. One of the main purposes of the DMSO is to act as a carrier for other drugs, enhancing their effects by facilitating skin penetration. Understanding the solubility and permeability of drugs in vivo is very important in drug discovery and development. Hence, this HER-NIRF technique has great potential to advance the utilization of the therapeutic agent DMSO by mapping its distribution via the solvatochromic shift of ICG. By customizing the operational wavelength range, this system can be applied to any other fluorophores in the near-infrared region and utilized for a wide variety of drug delivery studies. Full article

This study aimed to demonstrate the feasibility of ureteral navigation using intraoperative indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during complex laparoscopic or robot-assisted gynecologic surgery (LRAGS). Twenty-six patients at high risk of ureteral injury with complex pelvic pathology (CPP) due to pelvic organ prolapse (POP), multiple myomas, large intraligamentary or cervical myoma, severe pelvic adhesions, or cervical atresia underwent LRAGS. All patients underwent cystoscopic intraureteral ICG instillation before LRAGS and ureteral navigation under NIRF imaging intraoperatively. Both ureteral pathways were identified from the pelvic brim downwards through NIRF imaging in all patients, even though some were not visualized under the white light mode. The fluorescent ureters were visualized immediately after the beginning of surgery and typically lasted for >5 h during surgery. There were no cases of iatrogenic ureteral injury. The hemoglobin decrement was 1.47 ± 1.13 g/dL, and no transfusion was required. In our study, both ureters in all patients were identified with ICG-NIRF imaging during LRAGS, and these techniques made surgeries easier and safer. Despite the CPP, there was no ureteral injury or transfusion following surgery. Further prospective studies are needed to introduce intraoperative ureteral guidelines for ICG-NIRF imaging during LRAGS with CPP. Full article

Colorectal liver metastases (CRLM) afflict a significant proportion of patients with colorectal cancer (CRC), ranging from 25% to 30% of patients throughout the course of the disease. In recent years, there has been a surge of interest in the application of near-infrared fluorescence (NIRF) imaging as an intraoperative imaging technique for liver surgery. The utilisation of NIRF-guided liver surgery, facilitated by the administration of fluorescent dye indocyanine green (ICG), has gained traction in numerous medical institutions worldwide. This innovative approach aims to enhance lesion differentiation and provide valuable guidance for surgical margins. The use of ICG, particularly in minimally invasive surgery, has the potential to improve lesion detection rates, increase the likelihood of achieving R0 resection, and enable anatomically guided resections. However, it is important to acknowledge the limitations of ICG, such as its low specificity. Consequently, there has been a growing demand for the development of tumour-specific fluorescent probes and the advancement of camera systems, which are expected to address these concerns and further refine the accuracy and reliability of intraoperative fluorescence imaging in liver surgery. While NIRF imaging has been extensively studied in patients with CRLM, it is worth noting that a significant proportion of published research has predominantly focused on the detection of hepatocellular carcinoma (HCC). In this study, we present a comprehensive literature review of the existing literature pertaining to intraoperative fluorescence imaging in minimally invasive surgery for CRLM. Moreover, our analysis places specific emphasis on the techniques employed in liver resection using ICG, with a focus on tumour detection in minimal invasive surgery (MIS). Additionally, we delve into recent developments in this field and offer insights into future perspectives for further advancements. Full article

This comprehensive review aims to explore the applications of indocyanine green (ICG) in robot-assisted urological surgery through a detailed examination of fluorescence-guided techniques. An extensive literature search was conducted in PubMed/MEDLINE, EMBASE and Scopus, using keywords such as “indocyanine green,” “ICG”, “NIRF”, “Near Infrared Fluorescence”, “robot-assisted”, and “urology”. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. The integration of the Firefly^® technology in the Da Vinci^® robotic system has opened new avenues for the advancement and exploration of different urological procedures. ICG is a fluorophore widely used in near-infrared fluorescence-guided techniques. The synergistic combination of intraoperative support, safety profiles and widespread availability comprises an additional asset that empowers ICG-guided robotic surgery. This overview of the current state of the art illustrates the potential advantages and broad applications of combining ICG-fluorescence guidance with robotic-assisted urological surgery. Full article

Introduction: Successful R0 resection is crucial for the survival of patients with primary liver cancer (PLC) or liver metastases. Up to date, surgical resection lacks a sensitive, real-time intraoperative imaging modality to determine R0 resection. Real-time intraoperative visualization with near-infrared light fluorescence (NIRF) using indocyanine green (ICG) may have the potential to meet this demand. This study evaluates the value of ICG visualization in PLC and liver metastases surgery regarding R0 resection rates. Materials and Methods: Patients with PLC or liver metastases were included in this prospective cohort study. ICG 10 mg was administered intravenously 24 h before surgery. Real-time intraoperative NIRF visualization was created with the Spectrum^TM fluorescence imaging camera system. First, all liver segments were inspected with the fluorescence imaging system and intraoperative ultrasound for identification of the known tumor, as well as additional lesions, and were compared to preoperative MRI images. PLC, liver metastases, and additional lesions were then resected according to oncological principles. In all resected specimens, the resection margins were analyzed with the fluorescence imaging system for ICG-positive spots immediately after resection. Histology of additional detected lesions, as well as ICG fluorescence compared to histological resection margins, were assessed. Results: Of the 66 included patients, median age was 65.5 years (IQR 58.7–73.9), 27 (40.9%) were female, and 18 (27.3%) were operated on laparoscopically. Additional ICG-positive lesions were detected in 23 (35.4%) patients, of which 9 (29%) were malignant. In patients with no fluorescent signal at the resection margin, R0 rate was 93.9%, R1 rate was 6.1%, and R2 rate was 0% compared to an ICG-positive resection margin with an R0 rate of 64.3%, R1 rate of 21.4%, and R2 rate of 14.3% (p = 0.005). One- and two-year overall survival rates were 95.2% and 88.4%, respectively. Conclusion: The presented study provides significant evidence that ICG NIRF guidance helps to identify R0 resection intraoperatively. This offers true potential to verify radical resection and improve patient outcomes. Furthermore, implementation of NIRF-guided imaging in liver tumor surgery allows us to detect a considerable amount of additional malignant lesions. Full article

ASP5354 was recently developed as a near-infrared fluorescence (NIRF) contrast agent for intraoperative ureteral identification, and its use has been evaluated in healthy animals. However, the utilization of ASP5354 for ureteral identification has not been evaluated in animals with renal injury. In this study, we assessed the application of ASP5354 for ureteral imaging using rat models of gentamicin-induced mild, moderate, and severe acute kidney injury (AKI), using a clinically available NIRF detection system. NIRF was detected in the abdominal cavity and ureters after laparotomy, and the efficiency of ASP5354 was evaluated based on the NIRF signal intensity over 60 min. After the intravenous injection of ASP5354 into rats with mild or moderate AKI, the ureters were clearly imaged at a high ratio of NIRF intensity in the ureter to that in the tissues around the ureter. Six days after intravenous injection, the use of ASP5354 in rats with moderate AKI did not affect the biochemical kidney functions or histopathological conditions of the kidney tissues, as compared to those with no injection of ASP5354. In rats with severe AKI, ureteral imaging was not effective due to the relatively strong NIRF expression in the tissues around the ureters. These data indicate that ASP5354 holds potential as a contrast agent for intraoperative ureteral identification in patients with limited renal injury. Full article