Near-infrared Fluorescence Imaging Research Articles

IR-780 Dye-based Targeting of Cancer-associated Fibroblasts Improves Cancer Immunotherapy by Increasing Intra-tumoral T Lymphocytes Infiltration.

Immune-checkpoint inhibitors (ICIs) against programmed death (PD)-1/PD-L1 pathway immunotherapy have been demonstrated to be effective in only a subset of patients with cancer, while the rest may exhibit low response or may develop drug resistance after initially responding. Previous studies have indicated that extensive collagen-rich stroma secreted by cancer-associated fibroblasts (CAFs) within the tumor microenvironment is one of the key obstructions of the immunotherapy for some tumors by decreasing the infiltrating cytotoxic T cells. However, there is still a lack of effective therapeutic strategies to control the extracellular matrix by targeting CAFs. The enhanced uptake of IR-780 by CAFs was assessed by using in vivo or ex vivo nearinfrared fluorescence imaging, confocal NIR fluorescent imaging, and CAFs isolation testing. The fibrotic phenotype down-regulation effects and in vitro CAFs killing effect of IR-780 were tested by qPCR, western blot, and flow cytometry. The in vivo therapeutic enhancement of anti-PD-L1 by IR-780 was evaluated on EMT6 and MC38 subcutaneous xenograft mice models. IR-780 has been demonstrated to be preferentially taken up by CAFs and accumulate in the mitochondria. Further results identified low-dose IR-780 to downregulate the fibrotic phenotype, while high-dose IR-780 could directly kill both CAFs and EMT6 cells in vitro. Moreover, IR-780 significantly inhibited extracellular matrix (ECM) protein deposition in the peri-tumoral stroma on subcutaneous EMT6 and MC38 xenografts, which increased the proportion of tumor-infiltrating lymphocytes (TILs) in the deep tumor and further promoted anti-PD-L1 therapeutic efficacy. This work provides a unique strategy for the inhibition of ECM protein deposition in the tumor microenvironment by targeted regulating of CAFs, which destroys the T cell barrier and further promotes tumor response to PD-L1 monoclonal antibody. IR-780 has been proposed as a potential therapeutic small-molecule adjuvant to promote the effect of immunotherapy.

Pixel Screening in Lifetime-Based Temperature Mapping Using β-NaYF4:Nd3+,Yb3+ by Time-Gated Near-Infrared Fluorescence Imaging on Deep Tissue in Live Mice.

Near-infrared fluorescence (NIRF) thermometry is an emerging method for the noncontact measurement of in vivo deep temperatures. Fluorescence-lifetime-based methods are effective because they are unaffected by optical loss due to excitation or detection paths. Moreover, the physiological changes in body temperature in deep tissues and their pharmacological effects are yet to be fully explored. In this study, we investigated the potential application of the NIRF lifetime-based method for temperature measurement of in vivo deep tissues in the abdomen using rare-earth-based particle materials. β-NaYF4 particles codoped with Nd3+ and Yb3+ (excitation: 808 nm, emission: 980 nm) were used as NIRF thermometers, and their fluorescence decay curves were exponential. Slope linearity analysis (SLA), a screening method, was proposed to extract pixels with valid data. This method involves performing a linearity evaluation of the semilogarithmic plot of the decay curve collected at three delay times after cutting off the pulsed laser irradiation. After intragastric administration of the thermometer, the stomach temperature was monitored by using an NIRF time-gated imaging setup. Concurrently, a heater was attached to the lower abdomens of the mice under anesthesia. A decrease in the stomach temperature under anesthesia and its recovery via the heater indicated changes in the fluorescence lifetime of the thermometer placed inside the body. Thus, NaYF4:Nd3+/Yb3+ functions as a fluorescence thermometer that can measure in vivo temperature based on the temperature dependence of the fluorescence lifetime at 980 nm under 808 nm excitation. This study demonstrated the ability of a rare-earth-based NIRF thermometer to measure deep tissues in live mice, with the proposed SLA method for excluding the noisy deviations from the analysis for measuring temperature using the NIRF lifetime of a rare-earth-based thermometer.

Intraoperative Fluorescent Ureter Visualization for Transvaginal High Uterosacral Ligament Suspension for Severe Pelvic Organ Prolapse.

We aimed to demonstrate the feasibility of ureteral navigation using intra-ureteric indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during transvaginal high uterosacral ligament suspension for prolapse repair to reduce the risk of iatrogenic ureteral injury. A cystoscope was inserted into the bladder, the tip of a 6-F open-end ureteral catheter was inserted into the ureteral orifices, and ICG was instilled into the ureters. The ureteral path was then clearly identified using NIRF imaging. Sutures were safely placed in the uterosacral ligaments at the level of the ischial spine, taking advantage of direct ureteral visualization. At the end of the procedure, diagnostic cystoscopy was performed to confirm ureteral patency. No intraoperative or postoperative complications were observed. Intra-ureteric ICG-NIRF imaging represents a simple, inexpensive, and reproducible trick for intraoperative ureteral detection, and could reassure surgeons during difficult operations, for instance, in the case of severe prolapse and/or when ureteral course abnormalities are expected.

A preliminary investigation of precise visualization, localization, and resection of pelvic lymph nodes in bladder cancer by using indocyanine green fluorescence-guided approach through intracutaneous dye injection into the lower limbs and perineum

ObjectiveThis study aimed to investigate the feasibility and effectiveness of using indocyanine green (ICG) injected intracutaneously through the lower limbs and perineum for visualized tracking, localization, and qualitative assessment of pelvic lymph nodes (LNs) in bladder cancer to achieve their accurate resection.MethodsFirst, ICG was injected into the LN metastasis model mice lower limbs, and real-time and dynamic in vivo and ex vivo imaging was conducted by using a near-infrared fluorescence imaging system. Additionally, 26 patients with bladder cancer were enrolled and divided into intracutaneous group and transurethral group. A near-infrared fluorescence imaging device with internal and external imaging probes was used to perform real-time tracking, localization, and resection of the pelvic LNs.ResultsThe mice normal LNs and the metastatic LNs exhibited fluorescence. The metastatic LNs showed a significantly higher signal-to-background ratio than the normal LNs (3.9 ± 0.2 vs. 2.0 ± 0.1, p < 0.05). In the intracutaneous group, the accuracy rate of fluorescent-labeled LNs was 97.6%, with an average of 11.3 ± 2.4 LNs resected per patient. Six positive LNs were detected in three patients (18.8%). In the transurethral group, the accuracy rate of fluorescent-labeled LNs was 84.4%, with an average of 8.6 ± 2.3 LNs resected per patient. Two positive LNs were detected in one patient (12.5%).ConclusionFollowing the intracutaneous injection of ICG into the lower limbs and perineum, the dye accumulates in pelvic LNs through lymphatic reflux. By using near-infrared fluorescence laparoscopic fusion imaging, physicians can perform real-time tracking, localization, and precise resection of pelvic LNs.

Rising sun or strangled in the cradle？A narrative review of near-infrared fluorescence imaging-guided surgery for pancreatic tumors.

Near-infrared fluorescence (NIRF)-guided surgical navigation has become a promising and effective detection method in pancreatic tumor surgery. The imaging technique has gradually transitioned from the NIR-I region to the NIR-II region. Real-time assessment of the tumor boundary and determination of the ideal resection plane are essential for preserving the pancreatic parenchyma and its secretory functions. However, since the pancreatic parenchyma has a less rich blood supply than the liver, the application of contrast agents in pancreatic tumor surgery is still in its infancy. The application of indocyanine green (ICG) and methylene blue (MB) in intraoperative NIRF imaging of pancreatic tumors has become more mature, but due to the characteristics of non-specific imaging, the imaging efficiency and depth need to be improved. Many tumor-specific imaging agents have been designed, but most of them have not gone past animal trials because of their high development and imaging costs, biotoxicity, and other limitations. In this article, we review recent reports of ICG, MB and newly developed contrast agents and imaging devices. We focus on the current status and new developments in the application of these contrast agents and summarize the current clinical and preclinical studies on specific contrast agents. We synthesize relevant reports to discuss the difficulties and prospects of the application of fluorescent imaging agents in pancreatic tumors. We hope that reviewing previous studies and the current progress on contrast imaging technology will provide new perspectives for its future application and development in pancreatic tumor surgery, which should translate into better patient prognoses. The manuscript was written according to the Scale for the Assessment of Narrative Review Articles (SANRA).

Active Targeting Hyaluronan Conjugated Nanoprobe for Magnetic Particle Imaging and Near-Infrared Fluorescence Imaging of Breast Cancer and Lung Metastasis.

A major contributing cause to breast cancer related death is metastasis. Moreover, breast cancer metastasis often shows little symptoms until a large area of the organs is occupied by metastatic cancer cells. Breast cancer multimodal imaging is attractive since it integrates advantages from several modalities, enabling more accurate cancer detection. Glycoprotein CD44 is overexpressed on most breast cancer cells and is the primary cell surface receptor for hyaluronan (HA). To facilitate breast cancer diagnosis, we report an indocyanine green (ICG) and HA conjugated iron oxide nanoparticle (NP-ICG-HA), which enabled active targeting to breast cancer by HA-CD44 interaction and detected metastasis with magnetic particle imaging (MPI) and near-infrared fluorescence imaging (NIR-FI). When evaluated in a transgenic breast cancer mouse model, NP-ICG-HA enabled the detection of multiple breast tumors in MPI and NIR-FI, providing more comprehensive images and a diagnosis of breast cancer. Furthermore, NP-ICG-HAs were evaluated in a lung metastasis model. Upon NP-ICG-HA administration, MPI showed clear signals in the lungs, indicating the tumor sites. This is the first time that HA-based NPs have enabled MPI of cancer. NP-ICG-HAs are an attractive platform for noninvasive detection of primary breast cancer and lung metastasis.

Novel locally nebulized indocyanine green for simultaneous identification of tumor margin and intersegmental plane.

Segmentectomy, recommended for early-stage lung cancer or compromised lung function, demands precise tumor detection and intersegmental plane identification. While Indocyanine green (ICG) commonly aids in these aspects using near-infrared (NIR) imaging, its separate administrations through different routes and times can lead to complications and patient anxiety. This study aims to develop a lung-specific delivery method by nebulizing low-dose ICG to targeted lung segments, allowing simultaneous detection of lung tumors and intersegmental planes across diverse animal models. To optimizing the dose of ICG for lung tumor and interlobar fissure detection, different doses of ICG (0.25, 0.1 and 0.05mg/kg) were nebulized to rabbit lung tumor models. The distribution of locally nebulized ICG in targeted segments was studied to evaluate the feasibility of detecting lung tumor and intersegmental planes in canine lung pseudotumor models. NIR fluorescence imaging demonstrated clear visualization of lung tumor margin and interlobar fissure using local nebulization of 0.1mg/kg ICG for only 4 min during surgery in the rabbit models. In the canine model, the local nebulization of 0.05mg/kg of ICG into the target segment enabled clear visualization of pseudotumor and intersegmental planes for 30 min. This innovative approach achieves a reduction in ICG dose and prolonged the visualization time of the intersegmental plane and effectively eliminates the need for the hurried marking of tumors and intersegmental planes. We anticipate that lung specific delivery of ICG will prove valuable for image-guided limited resection of lung tumors in clinical practice.

Quantitative analysis of intestinal perfusion with indocyanine green (ICG) and methylene blue (MB) using a single clinically approved fluorescence imaging system: a demonstration in a porcine model.

Near-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB. Four mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25mg/kg-0.50mg/kg MB was administered after 10min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2mg/kg) after 60min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG. Intraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = -0.7709; p = < 0.001; r = -0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values. Our fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

A Dual-Cascade Activatable Near-Infrared Fluorescent Probe for Precise Intraoperative Imaging of Tumor.

Accurate intraoperative tumor delineation is critical to achieving successful surgical outcomes. However, conventional techniques typically suffer from poor specificity and low sensitivity and are time-consuming, which greatly affects intraoperative decision-making. Here, we report a cascade activatable near-infrared fluorescent (NIRF) probe IR780SS@CaP that can sequentially respond to tumor acidity and elevated glutathione levels for accurate intraoperative tumor localization. Compared with nonactivatable and single-factor activatable probes, IR780SS@CaP with a cascade strategy can minimize nonspecific activation and false positive signals in a complicated biological environment, affording a superior tumor-to-normal tissue ratio to facilitate the delineation of abdominal metastases. Small metastatic lesions that were less than 1 mm in diameter can be precisely identified by IR780SS@CaP and completely excised under NIRF imaging guidance. This study could benefit tumor diagnosis and image-guided tumor surgery by providing real-time information and reliable decision support, thus reducing the risk of both recurrence and complications to improve patient outcomes.

Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer

IntroductionColorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. MethodsA novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. ResultsThe CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. ConclusionThe favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

Targeted detection of Barrett’s neoplasia: A case report

Barrett&amp;rsquo;s esophagus (BE) is a precursor condition for esophageal adenocarcinoma (EAC). This case report describes the in vivo use of a fluorescently-labeled peptide heterodimer specific for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER2) to identify residual neoplasia in a 52-year-old female patient with BE. This targeted contrast agent was topically administered after an incomplete endoscopic mucosal resection of high-grade dysplasia with carcinoma in situ. A flexible fiber-coupled multi-modal scanning fiber endoscope was used to capture near-infrared fluorescence images. This instrument was passed through the working channel of a standard upper endoscope for use as an accessory. Increased fluorescence intensity was observed from nodular mucosa as a real-time &amp;ldquo;red flag&amp;rdquo; to identify the presence of neoplasia. Pathologic tests were conducted on the resected tissues, confirming the presence of stage T1a EAC. The expression EGFR and HER2 was confirmed by immunohistochemistry ex vivo. These findings support integrated imaging as a potential strategy to detect Barrett&amp;rsquo;s neoplasia.

Controlled In Situ Self-Assembly of Biotinylated Trans-Cyclooctene Nanoparticles for Orthogonal Dual-Pretargeted Near-Infrared Fluorescence and Magnetic Resonance Imaging.

A pretargeted strategy that decouples targeting vectors from radionuclides has shown promise for nuclear imaging and/or therapy in vivo. However, the current pretargeted approach relies on the use of antibodies or nanoparticles as the targeting vectors, which may be compromised by poor tissue penetration and limited accumulation of targeting vectors in the tumor tissues. Herein, we present an orthogonal dual-pretargeted approach by combining stimuli-triggered in situ self-assembly strategy with fast inverse electron demand Diels-Alder (IEDDA) reaction and strong biotin-streptavidin (SA) interaction for near-infrared fluorescence (NIR FL) and magnetic resonance (MR) imaging of tumors. This approach uses a small-molecule probe (P-Cy-TCO&Bio) containing both biotin and trans-cyclooctene (TCO) as a tumor-targeting vector. P-Cy-TCO&Bio can efficiently penetrate subcutaneous HeLa tumors through biotin-assisted targeted delivery and undergo in situ self-assembly to form biotinylated TCO-bearing nanoparticles (Cy-TCO&Bio NPs) on tumor cell membranes. Cy-TCO&Bio NPs exhibited an "off-on" NIR FL and retained in the tumors, offering a high density of TCO and biotin groups for the concurrent capture of Gd-chelate-labeled tetrazine (Tz-Gd) and IR780-labeled SA (SA-780) via the orthogonal IEDDA reaction and SA-biotin interaction. Moreover, Cy-TCO&Bio NPs offered multiple-valent binding modes toward SA, which additionally regulated the cross-linking of Cy-Gd&Bio NPs into microparticles (Cy-Gd&Bio/SA MPs). This process could significantly (1) increase r1 relaxivity and (2) enhance the accumulation of Tz-Gd and SA-780 in the tumors, resulting in strong NIR FL, bright MR contrast, and an extended time window for the clear and precise imaging of HeLa tumors.

High Rates of Discordant Ureteral Perfusion During Open Ureteral Reconstruction with Indocyanine Green: Does Near-Infrared Fluorescence Imaging Change Management or Stricture Outcomes?

OBJECTIVETo determine the role of near-infrared fluorescence imaging (NIFI) combined with indocyanine green (ICG) to assess ureteral tissue perfusion in a benign genitourinary reconstruction cohort with a high prevalence of prior abdominopelvic radiation and surgery. MATERIALS AND METHODSA prospective, single-surgeon series, between June 2018 and April 2022, of patients who underwent open genitourinary reconstructive surgeries in which NIFI/ICG was utilized to intraoperatively assess ureteral tissue perfusion prior to ureteral anastomosis. Primary outcome was ureteroanastomotic stricture (UAS). Secondary outcomes included impact of NIFI/ICG on surgical decision-making and ureter resection length. RESULTS39 patients, median age 66, underwent 40 multimodality reconstructive surgeries during which NIFI/ICG was utilized in the open setting. Radiation-induced etiology was present in 32 of 40 (80%) patients. UAS occurred in 1 of 57 (1.8%) anastomoses with median follow-up 23.4 months. Use of NIFI/ICG changed intraoperative decision-making in 63% of cases. Change in intraoperative decision-making was more common in patients with prior abdominopelvic radiation (66%) compared to non-radiated patients (13%), p=0.007. Discordance between subjective (white-light) and objective (NIFI/ICG) ureteral perfusion (white-light) occurred in 61% of ureters. Mean length of resected ureter was higher following objective assessment with NIFI/ICG (3.6 cm) versus subjective assessment (white light) conditions (1.8 cm), p=0.001. CONCLUSIONSUse of NIFI/ICG was associated with low rates of UAS at 2 years follow-up in a cohort with high prevalence of prior radiation. NIFI/ICG was associated with longer lengths of ureter resection and ureteral perfusion assessment discordance compared to subjective surgeon assessment under white-light conditions.

A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Engineering Cyanine- and Hemicyanine-Based Probes for Optical Imaging of Kidney Diseases.

Molecular optical probes paly pivotal roles in in vivo imaging of biomarkers associated to kidney diseases. Relying on structural tunability and high fluorescence quantum yields, versatile optical probes have been constructed on cyanine or hemicyanine-based scaffold in recent years. This review summaries the recent progress on the development of optical probes for imaging of kidney diseases, particularly through near-infrared fluorescence, chemiluminescence and photoacoustic imaging modalities. The chemical design and sensing mechanisms are discussed along with applications in the detection of renal cell carcinoma and acute kidney injury. This progress provides insights and directions for the development of next generation kidney-targeted probes and for pushing their further applications in preclinical and clinical research.

Depletion and Downregulation of Hydrogen Sulfide Using an Activatable Probe for Promoting Photothermal Therapy toward Colorectal Cancers.

Since hydrogen sulfide (H2S) is an important endogenous gaseous mediator, therapeutic manipulation of H2S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H2S-specific and photocontrolled synergistic activation for imaging-guided H2S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H2S-responsive molecule probe that can generate a cystathionine-β-synthase (CBS) inhibitor AOAA and a photothermal transducer into an NIR-light-responsive container. Our nanoplatform can turn on NIR fluorescence specifically in H2S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H2S-level downregulation. This smart regulation of the endogenous H2S level amplifies the PTT therapeutic effect, successfully suppressing colorectal tumor in living mice under NIR fluorescence imaging guidance. Thus, we believe that this nanoplatform may provide a powerful tool toward H2S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.

Fe3O4-Cy5.5-trastuzumab magnetic nanoparticles for magnetic resonance/near-infrared imaging targeting HER2 in breast cancer

This study developed a probe Fe3O4-Cy5.5-trastuzumab with fluorescence and magnetic resonance imaging functions that can target breast cancer with high HER2 expression, aiming to provide a new theoretical method for the diagnosis of early breast cancer. Fe3O4-Cy5.5-trastuzumab nanoparticles were combined with Fe3O4 for T2 imaging and Cy5.5 for near-infrared imaging, and coupled with trastuzumab for HER2 targeting. We characterized the nanoparticles used transmission electron microscopy, hydration particle size, Zeta potential, UV and Fourier transform infrared spectroscopy, and examined its magnetism, fluorescence, and relaxation rate related properties. CCK-8 and blood biochemistry analysis evaluated the biosafety and stability of the nanoparticles, and validated the targeting ability of Fe3O4-Cy5.5 trastuzumab nanoparticles through in vitro and in vivo cell and animal experiments. Characterization results showed the successful synthesis of Fe3O4-Cy5.5-trastuzumab nanoparticles with a diameter of 93.72 ± 6.34 nm. The nanoparticles showed a T2 relaxation rate 42.29 mM−1s−1, magnetic saturation strength of 27.58 emg g−1. Laser confocal and flow cytometry uptake assay showed that the nanoparticles could effectively target HER2 expressed by breast cancer cells. As indicated by in vitro and in vivo studies, Fe3O4-Cy5.5-trastuzumab were specifically taken up and effectively aggregated to tumour regions with prominent NIRF/MR imaging properties. CCK-8, blood biochemical analysis and histological results suggested Fe3O4-Cy5.5-trastuzumab that exhibited low toxicity to major organs and good in vivo biocompatibility. The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2 imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer.

Polydopamine-Coated Solid Silica Nanoparticles Encapsulating IR-783 Dyes: Synthesis and NIR Fluorescent Cell Imaging.

We report a simple and efficient synthetic method for polydopamine (PDA)-coated solid silica nanoparticles (s-SiO2@PDA NPs) encapsulating anionic near-infrared (NIR) fluorescent dyes through physical adsorption. Despite the use of anionic NIR fluorescent dyes indocyanine green (ICG) and 2-[2-[2-chloro-3-[2-[1,3-dihydro-3,3-dimethyl-1-(4-sulfobutyl)-2H-indol-2-ylidene]-ethylidene]-1-cyclohexen-1-yl]-ethenyl]-3,3-dimethyl-1-(4-sulfobutyl)-3H-indolium (IR-783), they were successfully immobilized on anionic s-SiO2@PDA NP surfaces under acidic aqueous conditions. After embedding in the s-SiO2@PDA NPs, the fluorescence of ICG was almost quenched, while a diminished IR-783 fluorescence remained observable. The fluorescence intensity of IR-783 embedded in s-SiO2@PDA NPs remained almost constant over 2 weeks in a pseudobiological solution, with a slight reduction due to dye degradation and dye leakage from the s-SiO2@PDA NPs. Finally, the s-SiO2@PDA NPs encapsulating IR-783 were successfully used for NIR fluorescent imaging of African green monkey kidney cells.

Detection and Real-Time Surgical Assessment of Colorectal Liver Metastases Using Near-Infrared Fluorescence Imaging during Laparoscopic and Robotic-Assisted Resections.

The European Association of Endoscopic Surgery (EAES) recommends, with strong evidence, the use of indocyanine green (ICG) fluorescence imaging combined with intraoperative ultrasound (IOUS) to improve identification of superficial liver tumors. This study reports the use of ICG for the detection of colorectal liver metastases (CRLMs) during minimally invasive liver resection. A single-center consecutive series of minimally invasive (laparoscopic and robotic) hepatic resections for CRLMs was prospectively evaluated (April 2019 and October 2023). A total of 25 patients were enrolled-11 undergoing laparoscopic and 14 undergoing robotic procedures. The median age was 65 (range 50-85) years. Fifty CRLMs were detected: twenty superficial, eight exophytic, seven shallow (<8 mm from the hepatic surface), and fifteen deep (>10 mm from the hepatic surface) lesions. The detection rates of CRLMs through preoperative imaging, laparoscopic ultrasound (LUS), ICG fluorescence, and combined modalities (ICG and LUS) were 88%, 90%, 68%, and 100%, respectively. ICG fluorescence staining allowed us to detect five small additional superficial lesions (not identified with other preoperative/intraoperative techniques). However, two lesions were false positive fluorescence accumulations. All rim fluorescence pattern lesions were CRLMs. ICG fluorescence was used as a real-time guide to assess surgical margins during parenchymal-sparing liver resections. All patients with integrity of the fluorescent rim around the CRLM displayed a radical resection during histopathological analysis. Four patients (8%) with a protruding rim or residual rim patterns had positive resection margins. ICG fluorescence imaging can be integrated with other conventional intraoperative imaging techniques to optimize intraoperative staging. Rim fluorescence proved to be a valid indicator of the resection margins: by removing the entire fluorescent area, a tumor-negative resection (R0) is achieved.

Rational Design of NIR-II G-Quadruplex Fluorescent Probes for Accurate In Vivo Tumor Metastasis Imaging.

Accurate in vivo imaging of G-quadruplexes (G4) is critical for understanding the emergence and progression of G4-associated diseases like cancer. However, existing in vivo G4 fluorescent probes primarily operate within the near-infrared region (NIR-I), which limits their application accuracy due to the short emission wavelength. The transition to second near-infrared (NIR-II) fluorescent imaging has been of significant interest, as it offers reduced autofluorescence and deeper tissue penetration, thereby facilitating more accurate in vivo imaging. Nonetheless, the advancement of NIR-II G4 probes has been impeded by the absence of effective probe design strategies. Herein, through a "step-by-step" rational design approach, we have successfully developed NIRG-2, the first small-molecule fluorescent probe with NIR-II emission tailored for in vivo G4 detection. Molecular docking calculations reveal that NIRG-2 forms stable hydrogen bonds and strong π-π interactions with G4 structures, which effectively inhibit twisted intramolecular charge transfer (TICT) and, thereby, selectively illuminate G4 structures. Due to its NIR-II emission (940 nm), large Stokes shift (90 nm), and high selectivity, NIRG-2 offers up to 47-fold fluorescence enhancement and a tissue imaging depth of 5 mm for in vivo G4 detection, significantly outperforming existing G4 probes. Utilizing NIRG-2, we have, for the first time, achieved high-contrast visualization of tumor metastasis through lymph nodes and precise tumor resection. Furthermore, NIRG-2 proves to be highly effective and reliable in evaluating surgical and drug treatment efficacy in cancer lymphatic metastasis models. We are optimistic that this study not only provides a crucial molecular tool for an in-depth understanding of G4-related diseases in vivo but also marks a promising strategy for the development of clinical NIR-II G4-activated probes.