Near-infrared Fluorescence Research Articles

Theranostic nanoemulsions suppress macrophage-mediated acute inflammation in rats

In inflammatory diseases or following an injury, dysregulated inflammation is a common driver of pain and tissue damage. Macrophages are immune cells that contribute to the initiation, maintenance, and resolution of inflammation due to their phenotypic plasticity in response to signals from inflammatory microenvironments. Macrophages infiltrate and polarize toward a pro-inflammatory phenotype (M1-like), thereby increasing the severity of inflammation. Therefore, we aimed to suppress the pro-inflammatory activity of M1-like macrophages and decrease their infiltration at the site of inflammatory insult to resolve tissue inflammation. To achieve this, we developed a theranostic curcumin-loaded nanoemulsion platform that delivers a low dose of curcumin, a known anti-inflammatory phytochemical, to macrophages and allows in vivo tracking of macrophages by near-infrared fluorescence (NIRF) imaging technique. In vitro, we showed that curcumin-loaded nanoemulsion suppressed polarization of macrophages towards M1-like phenotype, consequently decreasing the release of pro-inflammatory cytokines and mediators like IL-6, IL- TNF-, and nitric oxide (NO). Furthermore, curcumin-loaded nanoemulsion increased the level of IL-10, an anti-inflammatory cytokine, and protected macrophages against ferroptosis compared to drug-free nanoemulsion. In a rodent model of Complete Freund’s adjuvant (CFA)-induced inflammation, we demonstrated that infiltrating macrophages sequestered curcumin-loaded nanoemulsion droplets and acted as cellular drug depots at the site of inflammation. This consequently decreased macrophage infiltration at the CFA-induced inflammation site in both sexes compared to drug-free nanoemulsion, as demonstrated by NIRF imaging, H&E staining, and immunofluorescence. Taken together, our results indicated that the anti-inflammatory efficacy of curcumin was significantly improved when directly delivered to pro-inflammatory macrophages via theranostic nanoemulsion. This work opens an avenue for exploring theranostic nanoemulsions as a platform for delivering natural anti-inflammatory products for immune modulation.Graphical abstract

Discovery of Fatty Acid Translocase CD36-Targeting Near-Infrared Fluorescent Probe Enables Visualization and Imaging-Guided Surgery for Glioma.

Despite therapeutic advances in glioma, glioma-related mortality rates remain high due to its extremely poor prognosis and high recurrence. Near-infrared (NIR) fluorescence imaging technologies, using the clinically approved fluorescent probe 5-ALA, have gained prominence in facilitating visualization of glioma resection. However, the false-positive and false-negative results of 5-ALA decrease its sensitivity and specificity in detecting glioma, thereby hampering its use in glioma surgical navigation. Herein, a novel molecular probe MPA-Pip-abt-510 labeled with a NIR fluorescent dye MPA was developed, and its ability to target the CD36 protein, which is upregulated in glioma, was assessed. Fluorescent-labeled probes, conjugated to the CD36-targeting ligand abt-510, demonstrated high specificity and selectivity for CD36-positive tumor cells in vitro and tumor tissue in vivo. Biodistribution analysis of MPA-Pip-abt-510 revealed high tumor-specific accumulation in tumors, accompanied by minimal nonspecific uptake in background tissues, yielding a signal-to-noise ratio (SNR) of 6.6 ± 0.4 in a U87 subcutaneous glioma model 10 h postinjection. Meanwhile, quantitative analysis validated the high uptake of MPA-Pip-abt-510 in the U87 orthotopic tumor model, with a tumor-to-brain SNR of 5.4 ± 0.5, enabling the accurate identification of tumor tissue for surgical navigation. Moreover, pathological analysis of tumor and healthy brain tissues unveiled well-defined tumor boundaries, highlighting the capacity of the MPA-Pip-abt-510 probe to precisely visualize the CD36 protein at the molecular level. Given its rapid tumor-targeting abilities, durable retention, and accurate outlining of tumor boundaries, MPA-Pip-abt-510 emerges as a promising CD36-targeted fluorescence contrast agent and expands the toolbox of glioma fluorescent probes for surgical navigation.

NIR Fluorescence Strategy for the Early Diagnosis of Melanoma Liver Metastasis Based on the Cascade Reaction of Two Specific Bioenzymes.

Melanoma liver metastasis poses a serious risk to patient health, leading to deterioration of liver function accompanied by symptoms such as jaundice, abdominal pain, and weight loss. Early detection is paramount as it allows for timely intervention, potentially improving treatment efficacy and patient outcomes. Herein, a dual-target probe activated by butyrylcholinesterase (BChE) and tyrosinase (TYR) was proposed by initiating an enzyme cascade reaction, revealing NIR-emissive methylene blue (MB) as a responsive product. The cascade reaction mechanism was confirmed by enzyme activity inhibition experiments and high-resolution mass spectrometry. Intercellular imaging was carried out on the coincubation model of Hep G2 and B16 cell lines, which is the first attempt to the best of our knowledge. The results showed that BChE expressed in liver cells and TYR overexpressed in B16 cells jointly activated NIR fluorescence, which provides the possibility for the precise detection of melanoma liver metastasis. In vivo studies further proved that this method holds promise for the early diagnosis and postoperative adjunctive therapy of hepatic melanoma, ultimately enhancing survival rates.

DNA-Assembled Size-Permeable Microcapsule Bioreactor Enables Direct and Rapid Sensing of Trace Circulating MicroRNA Biomarkers in Undiluted Cancer Patient Serum.

Sensitive and direct detection of circulating microRNAs (miRNAs) in undiluted human serums can significantly facilitate the diagnosis of different diseases in the early stages; however, the achievement of such a goal is highly challenged by the extremely complex sample matrix nature of serums. Here, we show that sensitive and rapid detection of the circulating let-7a miRNA biomarker in undiluted cancer patient serums can be realized by a new size-permeable microcapsule bioreactor. The Cas13a/crRNA-dsDNA@polyethylene glycol core/shell biomicrocapsules are synthesized by simple encapsulation and etching steps. Such biomicrocapsules exhibit high stability, enhanced protein antifouling capability, and size-selective permeability that only allows short miRNA sequences to enter the core cavities, thereby enabling highly sensitive and direct detection of let-7a miRNA in undiluted serums down to 0.21 pM within 20 min via signal amplification by Cas13a/crRNA and near-infrared (NIR) fluorescence signals. The biomicrocapsule also allows unambiguous discrimination of the clear cell renal cell carcinoma patients from the healthy groups via direct detection of let-7a miRNA in the serum samples, thereby highlighting its robust clinical potential for early disease diagnoses.

A novel prostate cancer-specific fluorescent probe based on extracellular vesicles targeting STEAP1 applied in fluorescence guided surgery.

Radical prostatectomy with pelvic lymph node dissection is the best treatment for intermediate- to high-risk localized prostate cancer (PCa). However, conventional white light surgery has difficulties in identifying tumor boundary and micrometastases intraoperatively. Fluorescence guided surgery (FGS) can solve the above difficulties, but lacks tumor-specific near-infrared fluorescent (NIRF) probes in PCa. STEAP1 was an ideal target in PCa treatment and imaging. Here, we constructed a PCa specific fluorescent probe based on extracellular vesicles targeting STEAP1 (AS-EVs) loaded with NIRF dye S0456 and evaluated its preclinical profiles. In vitro and in vivo studies both showed S0456@AS-EVs was safe and showed strong targeting ability to PCa in various mice xenograft models. S0456@AS-EVs could clear rapidly from blood (half-time of 4.29 h) and retain in the STEAP1 positive tumor tissues for more than 72 h with the highest tumor background ratio (TBR) of 3:1, which was superior to ICG, free S0456, ICG@Ctrl-EVs and S0456@Ctrl-EVs (p < 0.01). Finally, S0456@AS-EVs was applied in FGS on intramuscular model, and the tumors were resected under white light and fluorescence respectively. Compared with white light surgery, mice undergoing FGS had lower positive margin rate and better postoperative survival (p = 0.0342).

NIFTy: near-infrared fluorescence (NIRF) imaging to prevent postsurgical hypoparathyroidism (PoSH) after thyroid surgery—a phase II/III pragmatic, multicentre randomised controlled trial protocol in patients undergoing a total or completion thyroidectomy

IntroductionPostsurgical hypoparathyroidism (PoSH) is an iatrogenic condition that occurs as a complication of several different procedures with thyroid surgery being the most common. PoSH has significant short- and long-term morbidities....

Application of a CYP1B1-Targeted NIR Probe for Breast Cancer Diagnosis, Surgical Navigation, and CYP1B1-Associated Chemotherapy Resistance Monitoring.

Early detection and precise treatment for breast cancer are crucial, given its high global incidence rate. Hence, the development of novel imaging targets is essential for diagnosing and monitoring resistance to chemotherapy, which is pivotal for achieving precise and personalized treatment for breast cancer patients. In our previous work, we successfully developed a near-infrared (NIR) probe 1 for CYP1B1-targeted imaging. In this study, we aimed to investigate the utility of the probe as a NIR fluorescence and photoacoustic dual-mode imaging probe for the detection and surveillance of breast cancer. Western blotting of cancer cell lines has confirmed that CYP1B1 is widely expressed in breast cancer and gynecological cancer. In vitro NIR fluorescence imaging capability of the probe for tracking CYP1B1-positive tumor cells was validated by using confocal microscopy. Further studies, including in vivo fluorescence and photoacoustic dual-model imaging and ex vivo biological distribution analysis on a triple-negative breast cancer xenograft mouse model, demonstrated that the probe selectively accumulated in tumor tissue within as early as 0.5 h postinjection. The results of the surgical resection experiment revealed that the tumor could be entirely removed under the guidance of NIR imaging, thereby indicating the probe's efficacy in surgical navigation. CYP1B1 expression was found to be upregulated in adriamycin (ADR)-resistant breast cancer cells, MCF-7/ADR. Consequently, the sensitivity of CYP1B1 overexpressed cells, MCF-7/1B1, to ADR was significantly reduced, with an IC50 value of 0.586 ± 0.0934 μM, compared to the parental MCF-7 cells with an IC50 value of 0.183 ± 0.0444 μM. In vivo and ex vivo imaging assays conducted on MCF-7/ADR tumor-bearing mice demonstrated that the probe was specifically enriched in tumor sites, suggesting its potential for monitoring chemotherapy resistance in breast cancer. This study expands the scope of application for NIR probe 1, establishing its utility in breast cancer diagnosis through fluorescence-photoacoustic dual-model imaging, monitoring of chemotherapy resistance, and guidance for surgical resection. This strategy paves the way for novel approaches to precise and personalized treatment for breast cancer patients.

PET-Based Dual-Modal Probes for In Vivo Imaging.

Molecular imaging has significantly advanced the detection and analysis of in vivo metabolic processes, while single-modal techniques remain limited. Dual-modal imaging, particularly positron emission tomography (PET)-based combinations has emerged as a powerful solution, offering enhanced capabilities through integration with magnetic resonance imaging (MRI) or near-infrared fluorescence (NIRF) imaging. This review highlights recent progress in PET-based dual-modal imaging, focusing on the development of various bimodal probes derived from antibodies, nanoparticles, and peptides, and key applications including image-guided surgery and disease assessment. PET-based dual-modal imaging holds substantial potential for advancing research and diagnostics by improving resolution and providing functional insights. By combining complementary modalities, these systems deliver a more comprehensive view of disease processes, leading to more accurate diagnoses and targeted treatments. Future research prioritizes optimizing probe design for enhanced biocompatibility and safety, facilitating clinical translation, and broadens applications beyond cancer. Through interdisciplinary collaboration, PET-based dual-modal probes are poised to play a pivotal role in improving patient outcomes, particularly in diagnosing and managing complex diseases.

Evaluating Postoperative Morbidity and Outcomes of Robotic-Assisted Esophagectomy in Esophageal Cancer Treatment—A Comprehensive Review on Behalf of TROGSS (The Robotic Global Surgical Society) and EFISDS (European Federation International Society for Digestive Surgery) Joint Working Group

Background: Esophageal cancer, the seventh most common malignancy globally, requires esophagectomy for curative treatment. However, esophagectomy is associated with high postoperative morbidity and mortality, highlighting the need for minimally invasive approaches. Robotic-assisted surgery has emerged as a promising alternative to traditional open and minimally invasive esophagectomy (MIE), offering potential benefits in improving clinical and oncological outcomes. This review aims to assess the postoperative morbidity and outcomes of robotic surgery. Methods: A comprehensive review of the current literature was conducted, focusing on studies evaluating the role of robotic-assisted surgery in esophagectomy. Data were synthesized on the clinical outcomes, including postoperative complications, survival rates, and recovery time, as well as technological advancements in robotic surgery platforms. Studies comparing robotic-assisted esophagectomy with traditional approaches were analyzed to determine the potential advantages of robotic systems in improving surgical precision and patient outcomes. Results: Robotic-assisted esophagectomy (RAMIE) has shown significant improvements in clinical outcomes compared to open surgery and MIE, including reduced postoperative pain, less blood loss, and faster recovery. RAMIE offers enhanced thoracic access, with fewer complications than thoracotomy. The RACE technique has improved patient recovery and reduced morbidity. Fluorescence-guided technologies, including near-infrared fluorescence (NIRF), have proven valuable for sentinel node biopsy, lymphatic mapping, and angiography, helping identify critical structures and minimizing complications like anastomotic leakage and chylothorax. Despite these benefits, challenges such as the high cost of robotic systems and limited long-term data hinder broader adoption. Hybrid approaches, combining robotic and open techniques, remain common in clinical practice. Conclusions: Robotic-assisted esophagectomy offers promising advantages, including enhanced precision, reduced complications, and faster recovery, but challenges related to cost, accessibility, and evidence gaps must be addressed. The hybrid approach remains a valuable option in select clinical scenarios. Continued research, including large-scale randomized controlled trials, is necessary to further establish the role of robotic surgery as the standard treatment for resectable esophageal cancer.

Accelerated Endosomal Escape of Splice-Switching Oligonucleotides Enables Efficient Hepatic Splice Correction.

Splice-switching oligonucleotides (SSOs) can restore protein functionality in pathologies and are promising tools for manipulating the RNA-splicing machinery. Delivery vectors can considerably improve SSO functionality in vivo and allow dose reduction, thereby addressing the challenges of RNA-targeted therapeutics. Here, we report a biocompatible SSO nanocarrier, based on redox-responsive disulfide cross-linked low-molecular-weight linear polyethylenimine (cLPEI), for overcoming multiple biological barriers from subcellular compartments to en-route serum stability and finally in vivo delivery challenges. Intracellularly responsive cross-links of cLPEI significantly accelerated the endosomal escape and offered efficient SSO release to the cell's nucleus, thereby leading to high splice correction in vitro. In vivo performance of cLPEI-SSOs was investigated in a novel transgenic mouse model for splice correction, spatiotemporal tracking of SSO delivery in wild-type mice, and biodistribution in a colorectal cancer peritoneal metastasis model. A single intravenous application of 5 mg kg-1 cLPEI-SSOs induced splice correction in liver, lung, kidney, and bladder, giving functional protein, which was validated by RT-PCR. Near-infrared (NIR) fluorescence imaging and X-ray computed tomography revealed improved organ retention and reduced renal excretion of SSOs. NIR microscopy demonstrated the accumulation of SSOs in angiogenic tumors within the pancreas. Successful nuclear delivery of SSOs was observed in the hepatocytes. Thus, cLPEI nanocarriers resulted in highly efficient splice correction in vivo, highlighting the critical role of the enhanced SSO bioavailability.

White Fluorescent Carbon Dots for Specific Fe3+ Detection and Imaging Applications.

In recent years, carbon dots (CDs) with fluorescence imaging function have been widely used in biomedicine, electronic manufacturing and environmental monitoring. However, monochromatic fluorescence is often limited by the application environment and loses its effectiveness. Here, we carefully designed white fluorescent CDs (WF-CDs) by solvothermal method, which is used for fluorescence imaging applications under different environmental conditions. WF-CDs based on nitrogen doping can produce obvious emission peaks at 400 nm, 490 nm and 640 nm, respectively, corresponding to red, green and blue (RGB) bands in the three primary colors. The full wavelength emission was realized by changing the solvent types and pH values to adjust the emission peak intensity. WF-CDs can accurately detect Fe3+ concentration according to fluorescence extinction degree (fluorescence elimination rate reaches 95.34%). Furthermore, WF-CDs has practical applications in cell-level fluorescence imaging, near-infrared fluorescence imaging and ultraviolet anti-counterfeiting, and has broad application prospects in the fields of nano-medicine and industrial manufacturing.

Near-infrared optical thermometry of nickel color centers in diamond.

We present an experimental study of temperature-dependent near-infrared fluorescence spectra of nickel color centers in diamond. The amplitude, the central wavelength, and the linewidth of the zero-phonon line (ZPL) in the fluorescence spectrum of these centers exhibit a strong temperature dependence, enabling highly sensitive temperature measurements. Due to the ZPL wavelength, falling within the biological transparency window, combined with a high-temperature sensitivity and low noise floor, as demonstrated by our experiments in practical thermometry settings, nickel color centers in diamond are ideally suited for all-optical temperature measurements, including thermometry of biological systems.

Near-Infrared Photothermally Assisted Nanoprobes Boost Signal Amplification for Fluorescence Imaging and Urinalysis of Tumor.

Early diagnosis of tumors allows effective treatment of primary cancers through localized therapeutic interventions. However, developing diagnostic tools for sensitive, simple, and early tumor (especially less than 2 mm in diameter) detection remains a challenge. Herein, we presented a biomarker-activatable nanoprobe that enabled a near-infrared (NIR) photothermally amplified signal for fluorescence imaging and urinalysis of tumor. This activatable nanoprobe was constructed by encapsulating renal-clearable NIR ZW800 dyes into a CuS@mSiO2 core-shell nanoparticle with hyaluronic acid. The nanoprobes could accumulate at the tumor site and respond to tumor-associated hyaluronidase, undergoing in situ enzyme-catalyzed decapsulation to release renal-clearable ZW800 dyes for fluorescence imaging and uranalysis of tumor in living mice. Notedly, with the aid of NIR laser irradiation, the photothermal effect of CuS core boosted signal amplification for tumor diagnosis via photothermally enhanced ZW800 release, providing high specificity and sensitivity. On account of the biomarker specificity and the spatiotemporally controlled NIR irradiation, the nanoprobes could selectively activate their NIR fluorescence (NIRF) signal to visualize tumors in living mice and allow for the easy translation of the nanoprobe as artificial urinary biomarker probes for in vitro diagnosis of tumor progression. In 4T1 tumor-bearing mice models, the activatable nanoprobes enabled ultrasensitive detection of tumors (1.9 mm in diameter). This study offers a noninvasive and photothermally signal-amplified approach for early tumor diagnosis via NIRF imaging or simple urine tests.

Sialic Acid-Modified NIR-II Fluorophore with Enhanced Brightness and Photoconversion Capability for Targeted Lymphoma Phototheranostics.

Lymphoma is a malignant cancer characterized by a rapidly increasing incidence, complex etiology, and lack of obvious early symptoms. Efficient theranostics of lymphoma is of great significance in improving patient outcomes, empowering informed decision-making, and driving medical innovation. Herein, we developed a multifunctional nanoplatform for precise optical imaging and therapy of lymphoma based on a new photosensitizer (1-oxo-1H-benzoo[de]anthracene-2,3-dicarbonitrile-triphenylamine (OBADC-TPA)). OBADC-TPA is a donor-acceptor (D-A) molecule characterized by a novel small coplanar and strong electron-withdrawing acceptor skeleton, while the OBADC moiety facilitates strong intramolecular charge transfer. OBADC-TPA-based nanoparticles (NPs) were prepared through encapsulation with an amphiphilic polymer and subsequent modification with sialic acid (SA). Both in vitro and in vivo studies demonstrated that NPs-SA possessed good biocompatibility, effective tumor accumulation, high photoacoustic (PA) contrast, bright second near-infrared (NIR-II) fluorescence emission, and efficient photothermal/photodynamic conversion capabilities, which can serve as a multifunctional nanocomposite for targeted PA/NIR-II fluorescence imaging-guided synergistic type I/II photodynamic and photothermal therapy (PDT/PTT) of lymphoma. This work not only provides a new NIR-II fluorophore with a novel acceptor moiety but also offers a new, accurate, and effective approach for the targeted diagnosis and treatment of lymphoma, holding promising prospects for clinical application.

Near-Infrared Fluorescence-Guided Segmentectomy: Added Benefit of Indocyanine Green Dye Diminishes With Surgeon Experience.

Near-infrared fluorescence (NIF)-mapping with indocyanine green dye (ICG) facilitates the identification of the intersegmental plane during minimally invasive segmentectomy. Our pilot study showed that ICG is associated with an increase in oncological margin distance from the tumour, greater than the surgeon's best judgment. We hypothesized that, with greater experience, the surgeon's judgement will improve, and the benefit of ICG will diminish. This is a phase 2 single-arm trial of patients undergoing robotic-assisted segmentectomy for NSCLC tumours less than 3cm. After isolating the diseased segment(s), the predicted intersegmental plane (Dp) was identified by the thoracic surgeon. After intravenous ICG injection, the true intersegmental plane (Dt) was revealed using NIF. The primary outcome was the average distance between Dt and Dp (Dt-Dp). Comparisons were performed across 3 temporal tertiles: tertile 1 (t1) comprised of the first 30 participants, and the remaining participants were divided equally for tertiles 2 (t2) and 3 (t3). Kruskal-Wallis test was used to compare differences between tertiles (α = 0.05). A total of 190 patients were enrolled from October 2016 to June 2021. The median age was 68 (interquartile range:62-72), and 57.37%(109/190) were women. ICG injection occurred in 60.53%(115/190) of the participants, and intersegmental plane visualization was achieved in 88.70%(102/115). Dt-Dp diminished significantly across tertiles: t1 = 20.65 ± 15.82mm, t2 = 2.42 ± 15.49mm, and t3 = 1.36 ± 9.87mm (P = 0.0001). Locally estimated scatterplot smoothing revealed that this distance approaches zero as the surgeon performs more cases. In our single-surgeon experience with robotic-assisted segmentectomy for NSCLC, the added value of NIF-mapping with ICG diminishes with surgeon experience.

Ischemic Area-Targeting and Self-Monitoring Nanoprobes Ameliorate Myocardial Ischemia/Reperfusion Injury by Scavenging ROS and Counteracting Cardiac Inflammation.

Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real-time monitoring of drug aggregation in the MIRI region remains an open question. Herein, a drug delivery system, hesperadin and ICG assembled in PLGA-Se-Se-PEG-IMTP (HI@PSeP-IMTP), is designed to deliver hesperadin and ICG to the MIRI region for in vivo optical imaging tracking and to ameliorate MIRI. The peak aggregation of nanoprobes in the MIRI region is monitored by near-infrared fluorescence and photoacoustic imaging. The maximal fluorescence and photoacoustic signals of the HI@PSeP-IMTP group in the MIRI region rise ≈32% and 40% respectively compared with that of HI@PSeP group. Moreover, HI@PSeP-IMTP effectively mitigates MIRI due to a synergistic integration of diselenide bonds and hesperadin, which can eliminate ROS and suppress cardiac inflammation. Specifically, the expression levels of p-CaMKII, p-IκBα, and p65 in the MIRI region in the HI@PSeP-IMTP group demonstrate a reduction of 30%, 46%, and 42% respectively compared to that of the PBS group. Collectively, HI@PSeP-IMTP provides new insights into the development of drugs integrating diagnosis and treatment for MIRI.

GLUT1 as a generic biomarker enables near-infrared fluorescence molecular imaging guided precise intraoperative tumor detection in breast cancer.

Precise tumor excision is important but challenging in breast-conserving surgery (BCS). Tumor-specific fluorescence imaging may be used for intraoperative tumor detection and, therefore, to guide precise tumor excision. The aims of this study are to develop a glucose transporter 1 (GLUT1)-targeted near-infrared fluorescence tracer and evaluate its accuracy for breast cancer detection using fresh surgical breast specimens. Bioinformatic analysis was performed to compare GLUT1 expression between breast cancer and normal breast tissues. A GLUT1-targeted fluorescence imaging tracer WZB117-CY7.5 was developed. In combination with fluorescence imaging (FMI), its binding specificity to GLUT1 was examined in in vitro breast cancer cell experiments, in vivo 4T1 breast tumor-bearing mouse models, and 60 freshly resected human breast tumor tissues. The diagnostic accuracy of WZB117-CY7.5, was evaluated in fresh specimens derived from 60 patients diagnosed with breast cancer. GLUT1 expression is higher in breast cancer tissues compared with normal tissues. WZB117-CY7.5 specifically bound to breast cancer cells in in vitro cell experiments and accumulated in tumor areas in a 4T1 tumor-bearing mice after intravenous injection by FMI. Moreover, WZB117-CY7.5 specifically bound to freshly resected human breast cancer and demonstrated excellent diagnostic performance in discriminating breast cancer, irrespective of cancer subtype, from normal breast tissue on fresh surgically resected breast tissues. WZB117-CY7.5 showed high accuracy in intraoperative breast cancer detection, irrespective of the cancer subtype. This highlights its potential for clinical applications as a generic tracer for fluorescence image-guided surgery (FIGS) in BCS and fluorescence image-guided pathology for tissue sampling.

Fibroblast activation protein peptide-targeted NIR-I/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma.

Cancer-associated fibroblasts (CAFs) are the primary stromal component of the tumor microenvironment in hepatocellular carcinoma (HCC), affecting tumor progression and post-resection recurrence. Fibroblast activation protein (FAP) is a key biomarker of CAFs. However, there is limited evidence on using FAP as a target in near-infrared (NIR) fluorescence imaging for HCC. Thus, this study aims to develop a novel NIR fluorescent imaging strategy targeting FAP+ CAFs in HCC. The ICG-FAP-TATA probe was synthesized by conjugating a novel cyclization anti-FAP peptide with an indocyanine green derivative (ICG-NH2) as fluorophore, capable for NIR window I (NIR-I, 700-900nm) and II (NIR-II, 1000-1700nm) imaging. Its efficacy in lesion localization and other potential applications was evaluated. In vivo imaging of subcutaneous HCC models revealed that ICG-FAP-TATA specifically targeted FAP+ CAFs in the stroma and detected differences in CAFs loading within lesions. The fluorescence intensity/tumor-to-background ratio (TBR) positively correlated with FAP expression (R2 > 0.8, p < 0.05). Ex vivo incubation of tumor tissues with ICG-FAP-TATA provided stable fluorescence imaging of tumors in subcutaneous and orthotopic HCC models, including different cell line co-culture systems (LM3-luc, MHCC97H-luc, HepG2-luc + LX2), and various liver backgrounds (healthy/fibrotic) (n = 5 per group). TBR of the tumor mice models was higher for NIR-II than NIR-I imaging (3.89 ± 1.27 vs. 2.64 ± 0.64, p < 0.05). Moreover, NIR-I/II imaging of fresh tissues from seven patients with HCC undergoing surgery incubated with ICG-FAP-TATA visually provided the spatial distribution heterogeneity of CAFs. The targeted fluorescence was relatively enriched more in the blood flow direction and at the tumor edge, both of which were associated with tumor metastasis (all p < 0.05). This study presents a rapid and effective method for detecting HCC lesions, locating FAP+ CAFs, and visualizing high-risk areas for tumor metastasis at the macroscopic level. It offers a new promising approach with translational potential for imaging HCC.

Controlled Introduction of sp3Quantum Defects in Fluorescent Carbon Nanotubes by Mechanochemistry.

Precise control over low-dimensional materials holds an immense potential for their applications in sensing, imaging and information processing. The controlled introduction of sp3 quantum defects (color centers) can be used to tailor the optoelectronic properties of single-walled carbon nanotubes (SWCNTs) in the tissue transparency (>800nm) and the telecommunication window. However, an uncontrolled functionalization of SWCNTs with defects leads to a loss of the NIR fluorescence. Here, we use mechanochemistry with aryldiazonium salts to create quantum defects in SWCNTs. The reaction proceeds within 5min without solvents or illumination and can be controlled by a varied mechanochemical energy impact. By working in the solid-state, this method presents an alternative synthetic route and marks a crucial step for tailoring photophysics of SWCNTs.

Development of Off-On Near-Infrared Fluorescent Probes for Sensitive In Vivo Imaging of Amyloid-β Species with Enhanced Pharmacokinetics.

The fluorescent imaging of pathologically accumulated β-amyloid (Aβ) proteins is of significant importance to the diagnosis of Alzheimer's disease (AD). In the paper, we prepare two new NIR probes, NIR-1 and NIR-2, through hydrophilic modification of introducing water-soluble bioactive groups such as polyethylene glycol (PEG) and morpholine to tune in vivo pharmacokinetics for specific detection of soluble and insoluble Aβ species. The in vitro assessments confirm that both NIR-1 and NIR-2 display strong near-infrared (NIR) fluorescence (FL) enhancement upon interaction with Aβ42 monomers, oligomers or aggregates (λem>670 nm) and show highly sensitive, rapid and selective response towards Aβ42 species. After i. v. injection, each probe showed fast blood-brain barrier (BBB) penetration and immediately produced intense FL signals in the brain of APP/PS1 AD model mice at 10 min. Moreover, compared with NIR-2, NIR-1 bearing a hydrophilic PEG chain displayed not only more rapid clearance but also lower background signal to efficiently distinguish APP/PS1 mice and wild-type mice with higher signal-to-background ratio, which was further validated by ex vivo histological staining of brain tissues. Therefore, due to its excellent pharmacokinetics, NIR-1 shows great promise as an effective NIR probe for specific detection of Aβ species.