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Keywords = near-infrared fluorescent dyes

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22 pages, 2486 KB  
Article
Cholesterol and Albumin as Key Modulators of ICG Photostability in Aqueous Solution
by Wiktoria Mytych, Mohammad A. Saad, Dorota Bartusik-Aebisher, David Aebisher and Gabriela Henrykowska
Molecules 2026, 31(15), 2738; https://doi.org/10.3390/molecules31152738 - 6 Aug 2026
Viewed by 337
Abstract
Indocyanine green (ICG) is a clinically approved near-infrared fluorescent dye used in medical imaging and diagnostics but has limitations owing to its poor photostability in aqueous environments. This paper has explored the role of human serum albumin (HSA) and cholesterol in protecting ICG [...] Read more.
Indocyanine green (ICG) is a clinically approved near-infrared fluorescent dye used in medical imaging and diagnostics but has limitations owing to its poor photostability in aqueous environments. This paper has explored the role of human serum albumin (HSA) and cholesterol in protecting ICG photostability. Pure ICG, an HSA-ICG complex, and an ICG–cholesterol colloidal assembly solution were stirred in the dark (control) and under continuous broadband irradiation (400–1600 nm, approximately 1.4 W), and absorption spectra (550–950 nm) were taken every 1 min, over 15 min. All the formulations were stable in the dark, with minimal total variance in absorbance. Pure ICG significantly photodegraded under irradiation (55 ± 2.75–65 ± 3.25% loss of maximum absorbance). The introduction of HSA and cholesterol limited the photodegradation, resulting in 15 ± 0.75–30 ± 1.5% and 25 ± 1.25% losses in maximum absorbance, respectively, upon irradiation. The modulators produced a significant increment in initial NIR absorbance (p < 0.001) and retained significantly high stability during irradiation (p < 0.01). Moreover, both modulators reduced photooxidative damage, as shown by the lower level of singlet oxygen (1O2) generation in the presence of HSA-ICG (35 ± 1.75%) and ICG–cholesterol (19 ± 0.95%) compared to pure ICG (57 ± 2.85% after 15 min). These results reveal that cholesterol is the best stabilizer of ICG photostability. By safely dissipating excitation energy via non-radiative decay, cholesterol demonstrates strong potential for enhancing ICG performance in photothermal therapy (PTT), whereas HSA remains the optimal modulator for near-infrared fluorescence imaging and photodynamic therapy. Full article
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36 pages, 28484 KB  
Review
Rare Earth-Doped Nanofluorescent Probes as Multifunctional Matrices for Advanced Biomedical Imaging
by Jiayi Guo, Hong-Bo Cui, Dong Liu, Chunzhi Li, Guijian Guan and Ming-Yong Han
Chemosensors 2026, 14(6), 134; https://doi.org/10.3390/chemosensors14060134 - 11 Jun 2026
Viewed by 587
Abstract
Benefiting from tunable emission from ultraviolet to near-infrared windows, long luminescence lifetimes, and exceptional photostability, rare earth (RE)-doped nanomaterials overcome the limitations of conventional dyes and quantum dots, enabling deep-tissue, high-resolution, and low-background imaging. As multifunctional fluorescent probes, RE-doped nanomaterials are driving the [...] Read more.
Benefiting from tunable emission from ultraviolet to near-infrared windows, long luminescence lifetimes, and exceptional photostability, rare earth (RE)-doped nanomaterials overcome the limitations of conventional dyes and quantum dots, enabling deep-tissue, high-resolution, and low-background imaging. As multifunctional fluorescent probes, RE-doped nanomaterials are driving the development of next-generation biomedical imaging. This review summarizes recent advances in the structural design of RE-doped nanomaterials, surface engineering for biocompatibility, and targeting strategies for improved performance, and highlights their integration into advanced imaging modalities, including NIR-I/II fluorescence, FLIM, PAI, super-resolution STED, multimodal FL/MRI/CT, X-ray-excited luminescence, and persistent luminescence. Meanwhile, mechanistic insights, material innovations, and comparative advantages are discussed. Furthermore, challenges related to quantum yield, scalable synthesis, imaging resolution, and clinical translation are considered, while future directions—centered on multifunctional probe design, NIR-II imaging, and AI-assisted data analysis—are proposed, offering a versatile platform for precise multimodal imaging with significant potential to advance early diagnosis, personalized therapy, and clinical applications. Full article
(This article belongs to the Special Issue Advanced Optical Imaging Technologies and Fluorescent Probes)
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25 pages, 323 KB  
Review
Near-Infrared Imaging in Small Animal Surgical Oncology: Current Applications and Future Directions
by Maureen A. Griffin
Animals 2026, 16(10), 1563; https://doi.org/10.3390/ani16101563 - 21 May 2026
Viewed by 559
Abstract
The use of near-infrared (NIR) fluorescence imaging has become increasingly widespread in the intraoperative management of human cancer patients, with diverse applications that enhance the visualization of tumors, metastatic lesions, draining lymph nodes, and critical anatomy. In recent years, the adoption of NIR [...] Read more.
The use of near-infrared (NIR) fluorescence imaging has become increasingly widespread in the intraoperative management of human cancer patients, with diverse applications that enhance the visualization of tumors, metastatic lesions, draining lymph nodes, and critical anatomy. In recent years, the adoption of NIR imaging in small animal surgical oncology has grown, with reported applications including nonselective and selective tumor imaging as well as sentinel lymph node (SLN) mapping for staging and surgical guidance. Despite these advances, clinical use in veterinary patients remains in its early stages, and further work is needed to define indications, optimize protocols, and determine its impact on outcomes. This review summarizes the current applications of NIR imaging in companion animal oncologic surgery, including techniques for dye administration, imaging agents, and reported clinical uses across tumor types. Key limitations are discussed, including limited tissue penetration, lack of tumor specificity with commonly used agents such as indocyanine green, variability in protocols, and limited data in certain species. Emerging technologies, including targeted fluorescent agents and advanced imaging approaches, are also highlighted. Overall, NIR imaging represents a promising adjunct in small animal surgical oncology, though further study and standardization are needed to support broader clinical integration. Full article
(This article belongs to the Special Issue Advances in Small Animal Surgical Oncology)
17 pages, 6198 KB  
Article
Substituent Effects on the Photophysical Properties of Neutral and Anionic Seminaphthofluorones: A Computational Study
by Stefania-Renata Stepanov and Vasile Chiș
Photochem 2026, 6(2), 16; https://doi.org/10.3390/photochem6020016 - 9 Apr 2026
Viewed by 501
Abstract
Seminaphtofluorones (SNAFRs) are a family of benzannulated xanthene dyes that exhibit strong fluorescence in both neutral and anionic states and can reach emission wavelengths in the deep-red to near-infrared region. Their optical response is highly sensitive to regioisomerism and functionalization, making them attractive [...] Read more.
Seminaphtofluorones (SNAFRs) are a family of benzannulated xanthene dyes that exhibit strong fluorescence in both neutral and anionic states and can reach emission wavelengths in the deep-red to near-infrared region. Their optical response is highly sensitive to regioisomerism and functionalization, making them attractive candidates for systematic structure–property investigations. Here, we computed the photophysical properties of six SNAFR regioisomers for both neutral and anionic species and correlate the calculated results with available experimental data. From the six dyes, we further chose two of them, SNAFR4 and SNAFR6, to further investigate how phenyl-ring functionalization modulates SNAFR properties by introducing methyl (–CH3) and carboxyl (–COOH) substituents at the ortho (o), meta (m), and para (p) positions. The calculations indicate that substitution induces measurable changes in geometries, as well as in excitation and emission energies, with particularly pronounced effects for the anionic derivatives. Overall, these results provide a computational framework for the rational tuning of SNAFRs’ optical properties and the design of derivatives with tailored optical characteristics for fluorescence imaging and applications in photodynamic therapy. Full article
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18 pages, 1671 KB  
Article
Preparation and Evaluation of Radiolabeled Porphyrin-Functionalized Lipid Nanodroplets for Cancer Theranostics
by Nur Izni Binti Ramzi, Kisa Tamamura, Masayuki Munekane, Kenji Mishiro, Takeshi Fuchigami, Xiaojun Hu, Renata Jastrząb, Seigo Kinuya, Kazuaki Ninomiya and Kazuma Ogawa
Molecules 2026, 31(7), 1114; https://doi.org/10.3390/molecules31071114 - 27 Mar 2026
Viewed by 804
Abstract
[111In]In-diethylenetriaminepentaacetic acid-5,10,15,20-tetraphenylporphyrin ([111In]In-DTPA-TPP) nanodroplets were developed for cancer theranostics, featuring ultrasound-sensitive properties. The designed nanodroplets that encapsulate the low-boiling-point liquid perfluorocarbon and IR-780 iodide, a near-infrared fluorescent dye, with surface conjugation of 111In-labeled porphyrin derivative, were synthesized and [...] Read more.
[111In]In-diethylenetriaminepentaacetic acid-5,10,15,20-tetraphenylporphyrin ([111In]In-DTPA-TPP) nanodroplets were developed for cancer theranostics, featuring ultrasound-sensitive properties. The designed nanodroplets that encapsulate the low-boiling-point liquid perfluorocarbon and IR-780 iodide, a near-infrared fluorescent dye, with surface conjugation of 111In-labeled porphyrin derivative, were synthesized and evaluated by in vitro and in vivo experiments. The cellular uptake of [111In]In-DTPA-TPP nanodroplets was significantly higher than that of control nanodroplets without TPP. Biodistribution experiments revealed greater tumor accumulation in mice injected with [111In]In-DTPA-TPP nanodroplets than in those injected with control nanodroplets lacking TPP. Additionally, the accumulation of [111In]In-DTPA-TPP nanodroplets in the tumor was visualized by single-photon emission computed tomography. Sonodynamic therapeutic experiments revealed that DTPA-TPP nanodroplets at 10 µmol total lipids/kg weight with a single ultrasound irradiation onto the tumor area significantly inhibited tumor growth. These results indicate that [111In]In-DTPA-TPP nanodroplets would be promising cancer theranostic agents. Full article
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45 pages, 4859 KB  
Review
Organic Dyes for Light-Based Biomedical Imaging and Therapy
by Panangattukara Prabhakaran Praveen Kumar
Colorants 2026, 5(2), 10; https://doi.org/10.3390/colorants5020010 - 26 Mar 2026
Cited by 1 | Viewed by 1474
Abstract
Light-based diagnostic and therapeutic approaches are increasingly important in modern biomedicine, with organic dyes emerging as versatile optical agents due to their tunable photophysical properties. Precise control over absorption and emission characteristics has enabled their application in fluorescence, photoacoustic, and Raman imaging, as [...] Read more.
Light-based diagnostic and therapeutic approaches are increasingly important in modern biomedicine, with organic dyes emerging as versatile optical agents due to their tunable photophysical properties. Precise control over absorption and emission characteristics has enabled their application in fluorescence, photoacoustic, and Raman imaging, as well as in photodynamic and photothermal therapies. However, challenges related to biocompatibility, aqueous stability, and in vivo performance remain critical for clinical translation. Organic dyes that absorb in the near-infrared region are particularly attractive because of their deeper tissue penetration and reduced background interference. This review highlights key structure property relationships of organic dyes and summarizes current design strategies, including chromophore modification, peripheral functionalization for water solubility, and self-assembled nanotheranostic systems. Recent biomedical applications in cancer diagnosis and therapy, bacterial detection, and imaging-guided treatment are discussed, along with future directions for advancing dye-based technologies in healthcare. Full article
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14 pages, 1566 KB  
Review
A Scoping Review on Fluorescence-Guided Surgery in Paediatric Renal Tumours: Current Perspectives and Future Plans
by Max Pachl and Valerie Rudolf von Rohr
Cancers 2026, 18(6), 1041; https://doi.org/10.3390/cancers18061041 - 23 Mar 2026
Cited by 1 | Viewed by 861
Abstract
Background/Objectives: Paediatric renal tumours, particularly Wilms tumours, have good survival outcomes following multimodal therapy; however, long-term morbidity related to nephrectomy and adjuvant treatment remains a major concern. As treatment paradigms increasingly prioritize nephron preservation and minimization of late effects, there is growing [...] Read more.
Background/Objectives: Paediatric renal tumours, particularly Wilms tumours, have good survival outcomes following multimodal therapy; however, long-term morbidity related to nephrectomy and adjuvant treatment remains a major concern. As treatment paradigms increasingly prioritize nephron preservation and minimization of late effects, there is growing interest in technologies that can enhance intraoperative precision. Methods: A scoping review following the PRISMA guidelines was performed. We analysed articles on fluorescence for childhood renal tumours on 1 November 2025. Case reports, opinion articles, and narrative reviews were excluded. An Ovid Medline search with search terms “Kidney neoplasm” AND “Fluorescent Dyes”, along with a Cochrane trials registry search for “kidney” AND “neoplasm” AND “Fluorescent Dye”, was performed, along with a hand search of citations. Results: The Ovid Medline search yielded 21 results, and the Cochrane trials search gave 4 results. Following review, five papers were included, of which one was an ex vivo study and one was a randomised, controlled trial that is currently recruiting. Conclusions: There is a lack of evidence around the use of near-infrared fluorescence in paediatric renal tumour surgery. This review summarizes the key current findings and future perspectives. Full article
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16 pages, 7199 KB  
Article
When Blue Turns the Green Off: Implications of Methylene Blue Interference in Indocyanine Green Near-Infrared Fluorescence Imaging
by Elisa Maria Gariboldi, Luigi Auletta, Roberta Ferrari, Alessandra Ubiali and Damiano Stefanello
Animals 2026, 16(6), 983; https://doi.org/10.3390/ani16060983 - 21 Mar 2026
Cited by 1 | Viewed by 928
Abstract
Sentinel lymph node mapping is increasingly used in canine and feline oncology and often involves the combined use of visible dyes and fluorescent tracers. However, the effect of methylene blue on the fluorescence of indocyanine green during near-infrared imaging remains unclear. This explorative [...] Read more.
Sentinel lymph node mapping is increasingly used in canine and feline oncology and often involves the combined use of visible dyes and fluorescent tracers. However, the effect of methylene blue on the fluorescence of indocyanine green during near-infrared imaging remains unclear. This explorative study aimed to quantitatively and qualitatively assess potential fluorescence quenching in solutions of methylene blue–indocyanine green at different ratios in three near-infrared imaging modalities (overlay, color map, contrast). Four solutions were prepared: 100%/0%, 75%/25%, 50%/50%, and 25%/75% indocyanine green/methylene blue. The fluorescence intensity of the four solutions was quantitatively measured in vitro using near-infrared imaging. Subsequently, four lymphographies, one for each solution, were performed from the metatarsal region of feline cadavers. Observers with varying levels of experience evaluated lymphographic images. Methylene blue caused a concentration-dependent reduction in fluorescence both at the quantitative evaluation and qualitative lymphography interpretation. Despite this reduction, fluorescence remained sufficient in cadavers for accurate identification of lymph nodes, and observer experience did not significantly affect interpretation, except for the color map mode. Because methylene blue-dominant solutions showed a greater quenching effect on indocyanine green fluorescence, clinicians should favor indocyanine green-dominant mixtures. This approach may preserve fluorescence performance, maintaining the surgical guidance benefits of methylene blue. Future confirmatory studies should include a substantially larger number of specimens to allow appropriate statistical comparisons and to better account for inter-individual variability. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Animal Oncology)
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16 pages, 10101 KB  
Article
Indocyanine Green as a Marker for Nose-to-Brain Delivery Pathways, Brain Distribution, and PLGA Nanoparticle Efficiency
by Milena Mishonova, Lea Koceva, Bissera Pilicheva, Plamen Zagorchev, Neli Raikova, Mitko Mladenov, Rossitza Konakchieva, Hristo Gagov and Iliyana Sazdova
Int. J. Mol. Sci. 2026, 27(4), 1782; https://doi.org/10.3390/ijms27041782 - 12 Feb 2026
Cited by 1 | Viewed by 753
Abstract
This study aims to assess the rate and duration of rat brain retention after a single intranasal administration of indocyanine green (ICG) as an aqueous solution or encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Near-infrared fluorescence emission of ICG from the brain and visceral organs [...] Read more.
This study aims to assess the rate and duration of rat brain retention after a single intranasal administration of indocyanine green (ICG) as an aqueous solution or encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Near-infrared fluorescence emission of ICG from the brain and visceral organs was measured at 1, 4, and 24 h, as well as at 1 and 2 weeks after administration. It was observed that both ICG formulations stained the olfactory bulbs and brainstem, the latter mainly in the basolateral region of the pons. Reduced staining was observed on day 7 after treatment, and the signal remains detectable on day 14. Additionally, while emission from ICG-labeled brains in water decreased after two weeks compared to day 7, in ICG-loaded nanoparticles, the emission was significantly higher on day 14. It is concluded that ICG is transported into the brain via both nose-to-brain delivery pathways—through and along olfactory or trigeminal nerves—and that ICG is a useful dye for in vivo studies due to its long-lasting emission and low toxicity. Furthermore, the suggested penetration of ICG-encapsulated PLGA nanoparticles via these transport mechanisms makes them a useful carrier for brain delivery of substances that are rapidly eliminated from circulation or do not cross the blood–brain barrier. Full article
(This article belongs to the Special Issue Advances in Research on Neurotransmitters)
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20 pages, 5919 KB  
Article
Optimization of Intraoperative Near-Infrared Fluorescence Mapping with Indocyanine Green for Sentinel Lymph Node Detection in Cervical and Endometrial Cancer
by Kanamat Efendiev, Maria Meshkova, Polina Alekseeva, Andrei Udeneev, Arkadii Moskalev, Maxim Loshchenov, Heda Maltsagova, Svetlana Mukhtarulina, Andrey Kaprin and Victor Loschenov
Pharmaceutics 2026, 18(2), 211; https://doi.org/10.3390/pharmaceutics18020211 - 6 Feb 2026
Viewed by 1439
Abstract
Background/Objectives: Lymph node dissection during surgeries for cervical and endometrial cancer is associated with significant complications and morbidity. Sentinel lymph nodes (SLNs) mapping using indocyanine green (ICG) has become a promising method for reducing surgical invasiveness and improving patient outcomes. However, the optimal [...] Read more.
Background/Objectives: Lymph node dissection during surgeries for cervical and endometrial cancer is associated with significant complications and morbidity. Sentinel lymph nodes (SLNs) mapping using indocyanine green (ICG) has become a promising method for reducing surgical invasiveness and improving patient outcomes. However, the optimal protocol for intraoperative fluorescence mapping of SLNs using ICG, especially regarding the timing of imaging after injection, remains to be fully optimized. This study aimed to evaluate the efficacy of real-time near-infrared (NIR) fluorescence SLN mapping at various time intervals and to investigate the photophysical properties of ICG in human lymph to establish a correlation between fluorescence signals and dye concentration. Methods: A prospective study included 20 patients with cervical and endometrial cancer undergoing laparoscopic or laparotomic surgery. Interstitial ICG injection was administered into the cervical stroma. SLN mapping was conducted using the novel VENERA-green endoscopic system (λexc = 800 nm, registration of fluorescence in the range of 830–1000 nm). Spectral fluorescence analysis (λexc = 650 nm) was conducted on SLNs and optical phantoms containing human lymph with ICG concentrations from 0 to 40 mg/L. The method made it possible to evaluate ICG absorption/emission properties, as well as to quantify concentration-dependent effects. Results: SLNs were successfully detected in all patients. The average detection time was 15 min with a range of 10 to 25 min. Fluorescence intensity of SLNs was significantly higher 10–15 min after ICG injection compared to 20–25 min. Spectral analysis indicated an absorption peak at 804 nm and an emission peak in the 835–855 nm range for ICG in human lymph. A concentration-dependent redshift of the fluorescence peak was observed and accurately modeled using a logarithmic function (R2 = 0.99), which allows for the estimation of ICG concentration in tissue. The bilateral detection rate was 77% for laparoscopy and 100% for laparotomy. Metastases were histologically confirmed in only 2.8% (1/36) of the detected SLNs. Conclusions: Intraoperative NIR fluorescence imaging using ICG is a highly sensitive method for real-time SLN mapping in gynecologic oncology. The optimal detection period is 10 to 15 min after cervical injection to achieve maximum ICG fluorescence intensity, compared to 20 to 25 min. The concentration-dependent fluorescence and absorption properties of ICG in lymph provide the basis for the development of quantitative intraoperative monitoring methods that could improve the accuracy of sentinel lymph node biopsy. Full article
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30 pages, 3219 KB  
Article
Indocyanine Green as a Theragnostic Agent in MCF-7 Breast Cancer Cells
by Wiktoria Mytych, Dorota Bartusik-Aebisher, Piotr Oleś, Aleksandra Kawczyk-Krupka, David Aebisher and Gabriela Henrykowska
Molecules 2026, 31(3), 520; https://doi.org/10.3390/molecules31030520 - 2 Feb 2026
Cited by 1 | Viewed by 1306
Abstract
Background/Objectives: Indocyanine green (ICG) is an FDA-approved, near-infrared fluorescent dye widely used for tumor imaging. This study aimed to evaluate the photodynamic efficacy and selectivity of ICG as a photosensitizer in photodynamic therapy (PDT) against MCF-7 breast cancer cells in 2D monolayers [...] Read more.
Background/Objectives: Indocyanine green (ICG) is an FDA-approved, near-infrared fluorescent dye widely used for tumor imaging. This study aimed to evaluate the photodynamic efficacy and selectivity of ICG as a photosensitizer in photodynamic therapy (PDT) against MCF-7 breast cancer cells in 2D monolayers and 3D collagen-embedded cell cultures that simulate ECM diffusion, and to confirm direct generation of singlet oxygen (1O2) as the primary cytotoxic species. Methods: MCF-7 breast adenocarcinoma cells and HMEC normal mammary epithelial cells were cultured in 2D monolayers, with MCF-7 cells additionally grown in 3D collagen type I matrices to mimic tumor environments. Cells were incubated with 50 µM ICG for 30 min, washed, and irradiated with a 780 nm diode laser at 39.8 mW/cm2. Cell viability was quantified using the Muse® Count & Viability assay at multiple time points, while ICG uptake and penetration were assessed via flow cytometry, fluorescence microscopy, and confocal imaging. Direct 1O2 production was measured through its characteristic 1270 nm phosphorescence using time-resolved near-infrared spectrometry. Results: ICG-PDT reduced MCF-7 viability to 58.3 ± 7.4% in 2D cultures (41.7% cell kill, p < 0.0001) and 70.2 ± 10.7% in 3D cultures (29.8% cell kill, p = 0.0002). In contrast, normal HMECs maintained 91.0 ± 1.3% viability (only 9% reduction, p = 0.08), resulting in a therapeutic index of approximately 4.6. IC50 values in 2D MCF-7 cultures decreased over time from 51.4 ± 3.0 µM at 24 h to 27.3 ± 3.0 µM at 72 h. ICG uptake was higher in 2D (78%) than in 3D (65%) MCF-7 cultures, with diffusion in 3D collagen exhibiting linear depth-dependent penetration. Notably, the singlet-oxygen phosphorescence signal, though weak and requiring highly sensitive detectors, provided direct evidence of efficient 1O2 generation. Conclusions: ICG as a photosensitizer in photodynamic therapy using clinically compatible parameters is highly cytotoxic to MCF-7 breast cancer cells while largely sparing HMECs in 2D cell culture. Direct spectroscopic evidence confirms efficient 1O2 generation, which contributes significantly to the cytotoxicity. The reduced efficacy in 3D versus 2D models highlights the importance of penetration barriers also present in solid tumors. These results support further preclinical and clinical investigation of ICG as a dual imaging-and-therapy (theragnostic) agent for selective photodynamic treatment of breast cancer. Full article
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17 pages, 8758 KB  
Article
From the Clinic, to the Clinic: Improving the Fluorescent Imaging Quality of ICG via Amphiphilic NIR-IIa AIE Probe
by Anjun Zhu, Zhibo Xiao, Aihui Sun, Feng Lu, Haozhou Tang, Xuekun Zhang, Ran Ren, Wei Yu, Andong Shao, Ninghan Feng, Shouyu Wang, Jianming Ni and Yaxi Li
Biosensors 2026, 16(2), 90; https://doi.org/10.3390/bios16020090 - 1 Feb 2026
Cited by 2 | Viewed by 855
Abstract
Fluorescence imaging is crucial for providing detailed information in clinical practice. However, traditional first near-infrared (NIR-I) dyes such as indocyanine green (ICG) exhibit limitations such as shallow penetration depth, low contrast, and suboptimal clarity due to light scattering and autofluorescence. To overcome these [...] Read more.
Fluorescence imaging is crucial for providing detailed information in clinical practice. However, traditional first near-infrared (NIR-I) dyes such as indocyanine green (ICG) exhibit limitations such as shallow penetration depth, low contrast, and suboptimal clarity due to light scattering and autofluorescence. To overcome these drawbacks, we utilized a novel amphiphilic second near-infrared (NIR-II) aggregation-induced emission (AIE) probe (TCP) with an emission range beyond 1300 nm (NIR-IIa). Using approximately 200 co-registered NIR-I/NIR-IIa image pairs acquired with TCP, we trained a SwinUnet-based deep learning model to transform low-quality NIR-I ICG images into high-resolution NIR-IIa-like images. Owing to its superior brightness and photostability, TCP enhances in vivo fluorescent angiography, offering clearer vascular details and a higher signal-to-background ratio (SBR) in the NIR-IIa region, 2.6-fold higher than that of ICG in the NIR-I region. The deep learning model successfully converted blurred NIR-I images into high-SBR NIR-IIa-like images, achieving rapid imaging speeds without compromising quality. This work introduces a synergistic “probe-plus-AI” paradigm that substantially improves both the quality and speed of clinical fluorescence imaging, providing a pathway that is immediately translatable to enhanced diagnostics and image-guided surgery. Full article
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52 pages, 16801 KB  
Review
Delving into the Inception of BODIPY Dyes: Paradigms of In Vivo Bioimaging, Chemosensing, and Photodynamic/Photothermal Therapy
by Olivia Basant, Edgardo Lobo, Gyliann Peña and Maged Henary
Pharmaceuticals 2026, 19(1), 169; https://doi.org/10.3390/ph19010169 - 18 Jan 2026
Cited by 8 | Viewed by 2526
Abstract
Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase [...] Read more.
Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes’ shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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29 pages, 9815 KB  
Article
Minimally Invasive Endovascular Administration for Targeted PLGA Nanoparticles Delivery to Brain, Salivary Glands, Kidney and Lower Limbs
by Olga A. Sindeeva, Lyubov I. Kazakova, Alexandra Sain, Olga I. Gusliakova, Oleg A. Kulikov, Daria A. Terentyeva, Irina A. Gololobova, Nikolay A. Pyataev and Gleb B. Sukhorukov
Pharmaceutics 2026, 18(1), 85; https://doi.org/10.3390/pharmaceutics18010085 - 9 Jan 2026
Viewed by 1620
Abstract
Background: While intravenous administration of nanoparticles (NPs) is effective for targeting the lungs and liver, directing them to other organs and tissues remains challenging. Methods: Here, we report alternative administration routes that improve organ-specific accumulation of poly (lactic-co-glycolic acid) (PLGA) NPs (100 nm, [...] Read more.
Background: While intravenous administration of nanoparticles (NPs) is effective for targeting the lungs and liver, directing them to other organs and tissues remains challenging. Methods: Here, we report alternative administration routes that improve organ-specific accumulation of poly (lactic-co-glycolic acid) (PLGA) NPs (100 nm, negatively charged) loaded with the near-infrared dye Cyanine 7 (Cy7). NP cytotoxicity was evaluated in HEK293, mMSCs, C2C12, L929, and RAW264.7 cells. Hemocompatibility was assessed using WBCs and RBCs. NPs were administered via the tail vein, carotid, renal, and femoral arteries in BALB/c mice. Administration safety was evaluated by laser speckle contrast imaging and histological analysis. NP biodistribution and accumulation were assessed using in vivo and ex vivo fluorescence tomography and confocal microscopy of cryosections. Results: PLGA-Cy7 NPs demonstrate low cytotoxicity even at high doses and exhibit good hemocompatibility. Administration of NPs through the mouse carotid, renal, and femoral arteries significantly increases accumulation in the target ipsilateral brain hemisphere (31.7-fold) and salivary glands (28.3-fold), kidney (13.7-fold), and hind paw (3.6-fold), respectively, compared to intravenous administration. Injection of NPs through arteries supplying the target organs and tissues does not result in significant changes in blood flow, morphological alterations, or irreversible embolization of vessels, provided the procedure is performed correctly and the optimal dosage is used. Conclusions: These results highlight the potential of intra-arterial delivery of NPs for organ-specific drug targeting, underscoring the synergistic impact of advances in materials science, minimally invasive endovascular surgery, and nanomedicine. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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30 pages, 1670 KB  
Review
Combining Fluorescence and Magnetic Resonance Imaging in Drug Discovery—A Review
by Barbara Smolak, Klaudia Dynarowicz, Dorota Bartusik-Aebisher, Gabriela Henrykowska, David Aebisher and Wiesław Guz
Pharmaceuticals 2026, 19(1), 56; https://doi.org/10.3390/ph19010056 - 26 Dec 2025
Cited by 2 | Viewed by 2531
Abstract
Drug discovery is a complex and multi-stage process that requires advanced analytical technologies capable of accelerating preclinical evaluation and improving the precision of therapeutic design. The combination of fluorescence and magnetic resonance imaging (MRI) within multimodal imaging plays an increasingly important role in [...] Read more.
Drug discovery is a complex and multi-stage process that requires advanced analytical technologies capable of accelerating preclinical evaluation and improving the precision of therapeutic design. The combination of fluorescence and magnetic resonance imaging (MRI) within multimodal imaging plays an increasingly important role in modern pharmacokinetics, integrating the high molecular sensitivity of fluorescence with the non-invasive anatomical visualization offered by MRI. Fluorescence enables real-time monitoring of cellular processes, including drug–target interactions and molecular dynamics, whereas MRI provides detailed structural information on tissues without exposure to ionizing radiation. Hybrid probes—such as superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with near-infrared (NIR) fluorophores or gadolinium-based complexes linked to optical dyes—enable simultaneous acquisition of molecular and anatomical data in a single examination. These multimodal systems are being explored in oncology, neurology, and cardiology, where they support improved visualization of tumor biology, amyloid pathology, and inflammatory processes in vascular disease. Although multimodal imaging shows great promise for enhancing pharmacokinetic and pharmacodynamic studies, several challenges remain, including the potential toxicity of heavy-metal-based contrast agents, limited tissue penetration of fluorescence signals, probe stability in vivo, and the complexity and cost of synthesis. Advances in nanotechnology, particularly biodegradable carriers and manganese-based MRI contrasts, together with the integration of artificial intelligence algorithms, are helping to address these limitations. In the future, fluorescence–MRI hybrid imaging may become an important tool in personalized medicine, supporting more precise therapy planning and reducing the likelihood of clinical failure. Full article
(This article belongs to the Special Issue Advances in Medicinal Chemistry: 2nd Edition)
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