Search Results (153)

Lymph node metastases are common in advanced ovarian cancer and are associated with poor prognosis. Accurate intraoperative identification of lymph node metastases remains a challenge in ovarian cancer surgery due to the lack of tumor-specific intraoperative imaging tools. Here, we developed a gonadotropin-releasing hormone receptor (GnRHR)-targeted near-infrared (NIR) fluorescent probe, GnRHa-PEG-Rh760, through conjugation of a GnRH analog peptide with the Rh760 fluorophore and polyethylene glycol (PEG). A non-targeted probe (PEG-Rh760) served as control. In mouse models of subcutaneous xenografts, peritoneal and lymph node metastases derived from ovarian cancer cells, GnRHa-PEG-Rh760 showed superior tumor-specific accumulation. NIR fluorescence imaging revealed strong fluorescence signals localized to primary tumors, peritoneal lesions, and metastatic lymph nodes with no off-target signals in normal lymph nodes. The spatial co-localization between the NIR fluorescence of GnRHa-PEG-Rh760 and tumor-derived bioluminescence clearly confirmed the probe’s target specificity. GnRHa-PEG-Rh760 mainly accumulated in the tumor and liver and was gradually cleared at 96 h post-injection. The retention of fluorescence signals in normal ovary tissue further validated GnRHR-mediated binding of the probe. Notably, GnRHa-PEG-Rh760 exhibited excellent biocompatibility with no observed systemic toxicity as evidenced by hematologic and histopathologic analyses. These data demonstrate the potential of GnRHa-PEG-Rh760 as an intraoperative imaging agent, providing real-time fluorescence imaging guidance to optimize surgical precision. This study highlights the value of receptor-targeted molecular imaging probes in precision cancer surgery. Full article

Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence tumor imaging by endoscopy to differentiate responders and the effect of nCRT on their expression. Methods: RC samples (n = 51) were collected from both pre-treatment biopsies and corresponding post-treatment surgical specimens. Samples were categorized by treatment response and determined using tumor regression grade (TRG) scoring. Immunohistochemistry assessed the expression of CEA, EpCAM, EGFR, and c-MET in tumors and adjacent normal tissues. Expression levels were quantified using H-scores (0–3), combining the percentage and intensity of stained cells. Pre- and post-treatment H-scores were compared to evaluate the impact of nCRT. Results: CEA, EpCAM, and c-MET were overexpressed in tumor tissue as compared to adjacent healthy mucosa in 100% (51/51), 98.4% (50/51), and 92% (47/51) of tumor biopsies, respectively, while EGFR showed no overexpression. A tumor-to-normal (T/N) ratio ≥ 2 was considered sufficient for differentiation in molecular fluorescence imaging. In pre-treatment biopsy samples, c-MET showed the highest T/N expression ratio (53% of the samples ≥ 2), followed by CEA (26.3%) and EpCAM (16%). Following nCRT treatment, CEA and c-MET maintained a ≥ 2 differential expression in 45% of all samples, whereas EpCAM exhibited this difference in only 9.2% of cases. Neoadjuvant therapy even significantly improved the T/N expression ratio for CEA and c-MET (p < 0.01) and EpCAM (p < 0.05), while EGFR expression remained lower than adjacent normal tissue. Significant increases in all marker expressions were observed in minimal responders (TRG4/5, p < 0.01–0.001), while near-complete responders (TRG2) exhibited non-significant changes in CEA, c-MET, and EGFR expression. Conclusions: c-MET and CEA emerged as optimal tumor imaging targets, showing sustained differential expression after nCRT. In vivo fluorescence-guided endoscopy using probes against these markers could play a role in future clinical decision-making. Full article

Near-infrared (NIR) rhodamine dyes are pivotal for bioimaging due to the minimal tissue interference. Yet, their rational design is hindered by unreliable computational methods for excited-state property prediction. We benchmarked the time-dependent density functional theory (TDDFT) with the linear-response (LR) and state-specific (SS) solvation models across five functionals (CAM-B3LYP, M06-2X, ωB97X-D, B3LYP, MN15) and optimized the ground/excited states for 42 rhodamine derivatives. A robust linear calibration framework was established by connecting the computed and experimental wavelengths, which was rigorously validated through six-fold cross-validation. The key metrics included the mean absolute error (MAE) and R² to assess the prediction robustness. CAM-B3LYP combined with LR solvation achieved the highest accuracy (absorption: MAE = 6 nm, R² = 0.94; emission: MAE = 12 nm, R² = 0.72). By integrating the TDDFT with a calibrated linear-response solvation model, we achieved sub-12 nm accuracy in predicting the NIR fluorescence peaks. This framework enabled the rational design of nine novel rhodamine derivatives with emissions beyond 700 nm, offering a paradigm shift in bioimaging probe development. Full article

With the increasing prevalence of plastic pollution, understanding its impact on soil nematodes is crucial for environmental sustainability and food security. Traditional fluorescence-based probes have the limitations of high background noise and interference from autofluorescence. In this study, the luminous upconverted NaYF4:Yb³⁺/Er³⁺ nanoparticles acted as high-sensitivity probes for real-time visualization of ingestion and biodistribution of polystyrene microplastics (PS-MPs) and nanoplastics (PS-NPs) in Caenorhabditis elegans. The novel probes enabled efficient near-infrared-to-visible light conversion. This approach improved the precision of nano- and microplastic detection in biological tissues. Microscopic imaging revealed that the probes effectively distinguished size-dependent plastic distribution patterns, with microplastics remaining in the digestive tract, whereas nanoparticles penetrated intestinal walls and entered systemic circulation. Quantitative fluorescence analysis confirmed that PS-NPs exhibited higher bioavailability and deeper tissue penetration, providing crucial insights into plastic behavior at the organismal level. The different toxicities of PS-NPs and PS-MPs were further confirmed by measurement of the locomotor impairments and the physiological disruptions. These findings emphasize the broader applications of upconverted nanoparticles as advanced bio-imaging probes, offering a sensitive and non-invasive tool for tracking pollutant interactions in environmental and biological systems. Full article

Peroxynitrite (ONOO⁻) is a reactive nitrogen species (RNS) that plays pivotal roles in various physiological and pathological processes. The recent literature has seen significant progress in the development of highly sensitive and selective fluorescent probes applicable for monitoring ONOO⁻ dynamics in live cells and a variety of animal models of human diseases. However, the clinical applications of those probes remain much less explored. This review delves into the biological roles of ONOO⁻ and summarizes the design strategies, sensing mechanisms, and bioimaging applications of near-infrared (NIR), long-wavelength, two-photon, and ratiometric fluorescent probes modified with a diverse range of functional groups responsive to ONOO⁻. Furthermore, we will discuss the remaining problems that prevent the currently developed ONOO⁻ probes from translating into clinical practice. Full article

H₂O₂ plays an important role in oxidative damage and redox signaling. Studies have shown that abnormal levels of H₂O₂ are closely related to the development of cancer. The levels of H₂O₂ in tumor cells are higher than in normal cells. Thus, it is of great importance to develop a fluorescent probe to monitor the level of H₂O₂ in vivo. This work reports a new biotin-guided NIR fluorescent probe, Bio-B-Cy, consisting of boronic acid ester as a H₂O₂-recognition site and biotin as a tumor binding site, which accelerates the fluorescence response to H₂O₂ in vivo. Bio-B-Cy exhibits good sensitivity and selectivity toward H₂O₂. In addition, Bio-B-Cy shows a dose-dependent response to H₂O₂ and the detection limit is 0.14 μM. We further demonstrate that Bio-B-Cy could successfully detect the H₂O₂ in biotin receptor-positive cancer cells and tumor tissues. Based on the results, Bio-B-Cy has the potential to serve as an efficient tool for early diagnosis of cancer. Full article

Near-infrared (NIR) light is a promising tool for biomedical imaging and therapy, offering excellent tissue penetration, low scattering, and minimal biological fluorescence interference. An NIR-II optical range of 900–1880 nm with reduced background interference is particularly useful for disease diagnosis and treatment. Probes based on organic molecules are gaining attention for their structural flexibility and stable performance. Organic molecular aggregates, such as J-aggregates, H-aggregates, and aggregation-induced emission (AIE)-aggregates, exhibit unique optical properties like tunable spectral shifts, improved photostability, and higher absorption and fluorescence quantum yields. This mini review briefly discusses the advancements in NIR-II optical imaging and therapy technologies, focusing on the classification, formation mechanisms, and applications of organic molecular aggregates in disease diagnosis and treatment, offering a theoretical foundation and practical guidance for future research. Full article

Stroke, primarily ischemic (85%), results from inadequate blood supply and is worsened by ferroptosis, characterized by free radical generation and lipid peroxidation. Monitoring ferroptosis is essential for understanding its mechanisms and developing treatments. Glutathione (GSH) is a key ferroptosis biomarker, but current probes are limited by short excitation/emission wavelengths, small Stokes shifts, and inability to monitor dynamic GSH changes at the cellular membrane, where ferroptosis plays a crucial role. To address these issues, we developed the PM-Red-GSH, a novel near-infrared (NIR) probe based on the Excited-state intramolecular proton transfer (ESIPT) mechanism. It shows strong NIR emission (715 nm), large Stokes shift (290 nm), and enhanced membrane binding (PCC = 0.95) due to its alkyl group. PM-Red-GSH enables dynamic GSH monitoring in an MCAO mouse model. These findings offer new insights into ferroptosis and stroke treatment. Full article

The use of biomass feedstocks for producing high-value-added chemicals is gaining significant attention in the academic community. In this study, near-infrared carbon dots (NIR-CDs) with antimicrobial and bioimaging functions were prepared from Epigynum auritum branches and leaves using a novel green synthesis approach. The spectral properties of the synthesized NIR-CDs were characterized by ultraviolet–visible (UV-Vis) absorption and fluorescence spectroscopy. The crystal structures of the NIR-CDs were further characterized by high-resolution transmission electron microscopy (HR-TEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), and X-ray diffraction (XRD). The NIR-CDs exhibited minimal toxicity, excellent biocompatibility, and high penetrability in both in vivo and in vitro environments, making them ideal luminescent probes for bioimaging applications. Moreover, the antimicrobial activity of NIR-CDs was tested against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), showing significant bacterial growth inhibition. The antimicrobial effect is likely attributed to the NIR-CDs disrupting the cell membrane integrity, leading to the leakage of the intracellular contents. Therefore, NIR-CDs hold promise as fluorescent bioimaging probes and antimicrobial agents. Full article

Bright biocompatible fluorescent imaging dyes with red to near-infrared (NIR) emissions are ideal candidates for fluorescence microscopy applications. Pyrene–benzothiazolium hemicyanine dyes are a new class of lysosome-specific probes reported on recently. In this work, we conduct a detailed implementation study for a pyrene–benzothiazolium derivative, BTP, to explore its potential imaging applications in fluorescence microscopy. The optical properties of BTP are studied in intracellular environments through advanced fluorescence microscopy techniques, with BTP exhibiting a noticeable shift toward blue (λ_em ≈ 590 nm) emissions in cellular lysosomes. The averaged photon arrival time (AAT)-based studies exhibit two different emissive populations of photons, indicating the probe’s dynamic equilibrium between two distinctively different lysosomal microenvironments. Here, BTP is successfully utilized for time-lapse fluorescence microscopy imaging in real-time as a ‘wash-free’ imaging dye with no observed background interference. BTP exhibits an excellent ability to highlight microorganisms (i.e., bacteria) such as Bacillus megaterium through fluorescence microscopy. BTP is found to be a promising candidate for two-photon fluorescence microscopy imaging. The two-photon excitability of BTP in COS-7 cells is studied, with the probe exhibiting an excitation maximum at λ_TP ≈ 905 nm. Full article

In this paper, LD-TCF, a targeting probe for lipid droplets (LDs) with a near-infrared emission wavelength and large Stokes shift, was fabricated for polarity detection by assembling a donor–π–acceptor (D–π–A) molecule with typical twisted intramolecular charge transfer (TICT) characteristics. Surprisingly, the fluorescence emission wavelength of the newly constructed probe LD-TCF was stretched to 703 nm, and the Stokes shift was amplified to 126 nm. Furthermore, LD-TCF could specifically answer the change in polarity efficiently and did not experience interference from other biologically active materials. Importantly, LD-TCF exhibited the ability to target lipid droplets, providing valuable insights for the early diagnosis and tracking of pathophysiological processes underlying LD polarity. Full article

Background/Objectives: Pancreatic cancer is the third leading cause of death related to cancer. The only possible cure presently is complete surgical resection; however, this is limited by difficulty in clearly defining tumor margins. Enhancement of the visualization of pancreatic ductal adenocarcinoma (PDAC) tumor margins using near-infrared dye-conjugated tumor-specific antibodies was pioneered by using anti-CEA, anti-CA19.9, and anti-MUC5AC in orthotopic mouse models of pancreatic cancer. Recently, an antibody to Mucin 4 (MUC4) conjugated to a fluorescent probe has shown promise in targeting colon tumors in orthotopic mouse models. Methods: In the present study, we targeted pancreatic cancer using an anti-MUC4 antibody conjugated to IRDye800 (anti-MUC4-IR800) in orthotopic mouse models. Two pancreatic cancer human cell lines were used, SW1990 and CD18/HPAF. Results: Anti-MUC4-IR800 targeted the two pancreatic cancer cell line tumors in orthotopic mouse models with high tumor-to-pancreas ratios and high tumor-to-liver ratios, with greater targeting seen in SW1990. Conclusions: The present results suggest anti-MUC4-IR800’s potential to be used in fluorescence-guided surgical resection of pancreatic cancer. Full article

Lung cancer is a major threat to human health and a leading cause of death. Accurate localization of tumors in vivo is crucial for subsequent treatment. In recent years, fluorescent imaging technology has become a focal point in tumor diagnosis and treatment due to its high sensitivity, strong selectivity, non-invasiveness, and multifunctionality. Molecular probes-based fluorescent imaging not only enables real-time in vivo imaging through fluorescence signals but also integrates therapeutic functions, drug screening, and efficacy monitoring to facilitate comprehensive diagnosis and treatment. Among them, near-infrared (NIR) fluorescence imaging is particularly prominent due to its improved in vivo imaging effect. This trend toward multifunctionality is a significant aspect of the future advancement of fluorescent imaging technology. In the past years, great progress has been made in the field of NIR fluorescence imaging for lung cancer management, as well as the emergence of new problems and challenges. This paper generally summarizes the application of NIR fluorescence imaging technology in these areas in the past five years, including the design, detection principles, and clinical applications, with the aim of advancing more efficient NIR fluorescence imaging technologies to enhance the accuracy of tumor diagnosis and treatment. Full article

NO is a crucial signaling molecule involved in skin health, the immune response, and the protection against environmental stressors. This study explores how different wavelengths of light, namely blue (455 nm), red (660 nm), and near infrared (NIR, 850 nm), affect nitric oxide (NO) production in skin cells. Primary keratinocytes and fibroblasts from three donors were exposed to these wavelengths, and NO production was quantified using a DAF-FM fluorescent probe. The results demonstrated that all three wavelengths stimulated NO release, with blue light showing the most pronounced effect. Specifically, blue light induced a 1.7-fold increase in NO in keratinocytes compared to red and NIR light and a 2.3-fold increase in fibroblasts compared to red light. Notably, fibroblasts exposed to NIR light produced 1.5 times more NO than those exposed to red light, while keratinocytes consistently responded more robustly across all wavelengths. In conclusion, blue light significantly boosts NO production in both keratinocytes and fibroblasts, making it the most effective wavelength. Red and NIR light, while less potent, also promote NO production and could serve as complementary therapeutic options, particularly for minimizing potential photoaging effects. Full article

As one of the leading cancers threatening women’s lives and health, breast cancer is challenging to treat and often irreversible in advanced cases, highlighting the critical importance of early detection and intervention. In recent years, fluorescent probe technology, a revolutionary in vivo imaging tool, has gained attention in medical research for its ability to improve tumor visualization significantly. This review focuses on recent advances in intelligent, responsive fluorescent probes, particularly in the field of breast cancer, which are divided into five categories, near-infrared responsive, fluorescein-labeled, pH-responsive, redox-dependent, and enzyme-triggered fluorescent probes, each of which has a different value for application based on its unique biological response mechanism. In addition, this review also covers the strategy of combining fluorescent probes with various anti-tumor drugs, aiming to reveal the possibility of synergistic effects between the two in breast cancer treatment and provide a solid theoretical platform for the clinical translation of fluorescent probe technology, which is expected to promote the expansion of cancer treatment technology. Full article