Infrared Fluorescence Research Articles

A pan-cancer dye for solid-tumour screening, resection and wound monitoring via short-wave and near-infrared fluorescence imaging.

The efficacy of fluorescence-guided surgery in facilitating the real-time delineation of tumours depends on the optical contrast of tumour tissue over healthy tissue. Here we show that CJ215-a commercially available, renally cleared carbocyanine dye sensitive to apoptosis, and with an absorption and emission spectra suitable for near-infrared fluorescence imaging (wavelengths of 650-900 nm) and shortwave infrared (SWIR) fluorescence imaging (900-1,700 nm)-can facilitate fluorescence-guided tumour screening, tumour resection and the assessment of wound healing. In tumour models of either murine or human-derived breast, prostate and colon cancers and of fibrosarcoma, and in a model of intraperitoneal carcinomatosis, imaging of CJ215 with ambient light allowed for the delineation of nearly all tumours within 24 h after intravenous injection of the dye, which was minimally taken up by healthy organs. At later timepoints, CJ215 provided tumour-to-muscle contrast ratios up to 100 and tumour-to-liver contrast ratios up to 18. SWIR fluorescence imaging with the dye also allowed for quantifiable non-contact wound monitoring through commercial bandages. CJ215 may be compatible with existing and emerging clinical solutions.

Multicolor Tuning of Perylene Diimides Dyes for Targeted Organelle Imaging In Vivo.

The adjustment of the emission wavelengths and cell permeability of the perylene diimides (PDI) for multicolor cell imaging is a great challenge. Herein, based on a bay-region substituent engineering strategy, multicolor perylene diimides (MCPDI) were rationally designed and synthesized by introducing azetidine substituents on the bay region of PDIs. With the fine-tuned electron-donating ability of the azetidine substituents, these MCPDI showed high brightness, orange, red, and near infrared (NIR) fluorescence along with Stokes shifts increasing from 35 to 110 nm. Interestingly, azetidine substituents distorted to the plane of the MCPDI dyes, and the twist angle of monosubstituted MCPDI was larger than that of disubstituted MCPDI, which might efficiently decrease their π-π stacking. Moreover, all of these MCPDI dyes were cell-permeable and selectively stained various organelles for multicolor imaging of multiple organelles in living cells. Two-color imaging of lipid droplets (LDs) and other organelles stained with MCPDI dyes was performed to reveal the interaction between the LDs and other organelles in living cells. Furthermore, a NIR-emitting MCPDI dye with a mitochondria-targeted characteristic was successfully applied for tumor-specific imaging. The facile synthesis, excellent stability, high brightness, tunable fluorescence emission, and Stokes shifts make these MCPDI promising fluorescent probes for biological applications.

A Review of Image Sensors Used in Near-Infrared and Shortwave Infrared Fluorescence Imaging.

To translate near-infrared (NIR) and shortwave infrared (SWIR) fluorescence imaging into the clinic, the paired imaging device needs to detect trace doses of fluorescent imaging agents. Except for the filtration scheme and excitation light source, the image sensor used will finally determine the detection limitations of NIR and SWIR fluorescence imaging systems. In this review, we investigate the current state-of-the-art image sensors used in NIR and SWIR fluorescence imaging systems and discuss the advantages and limitations of their characteristics, such as readout architecture and noise factors. Finally, the imaging performance of these image sensors is evaluated and compared.

Controlled dual activity of an organometallic antibiotic through micelle formulation

Sodium Lauryl Sulphate (SLS) and Cetyltrimethylammonium bromide (CTAB) were employed to create micelles (SLS@CIPTIN and CTAB@CIPTIN) of the organometallic antibiotic Ph2Sn(CIP)2 (CIPTIN) (where HCIP= ciprofloxacin). The characterization of the micelles was conducted in the solid-state using melting point, Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR), 119Sn Mössbauer and X-ray Fluorescence (XRF) spectroscopies, and Thermogravimetry/Differential Thermal Analysis (TG-DTA), while in solution, by Ultra violet-Visible (UV–Vis) and Nucleus Magnetic Resonance (1HNMR ) spectroscopic techniques were employed. The compounds were tested for their antiproliferative activity against human breast adenocarcinoma cells: MCF-7 (hormone depended (HD)) and MDA-MB-231 (hormone independent (HI)). The in vitro and in vivo non-genotoxicity was confirmed with micronucleus (MN) and Artemia salina assay. The antiproliferative mechanism of action of SLS@CIPTIN and CTAB@CIPTIN was studied by cell morphology and cell cycle arrest. The antibacterial activity was evaluated using Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZ) against Minimum Bactericidal Concentration (MBC) against Gram-negative strains P. aeruginosa, E. coli, as well as Gram-positive strains S. epidermidis and S. aureus. The results indicate that both the investigated CIPTIN and its supramolecular assembly (SLS@CIPTIN) exhibit activity. Therefore, the encapsulation of antimicrobial compounds can indeed be regarded as an attractive strategy for the development of new dual-active agents. These agents offer concurrent anticancer and antibacterial attributes without inducing toxicity.

Effect of glycation-induced concentration-dependent change in albumin structure and alteration in its binding capacity

Reducing sugars causes confirmatory alterations in albumin structure by the nonenzymatic glycation of the amino group of serum albumin. In this study, glucose and its hazardous metabolic products like glyoxal and methylglyoxal were incubated with bovine serum albumin (BSA). The confirmational changes in BSA molecule’s structure by glycating substances was investigated using a variety of spectroscopic methods, including deconvolutionFourier Transform Infra-red (FT-IR) spectroscopy, fluorescence spectroscopy, UV spectroscopy and circular dichroism (CD) spectroscopy. Dynamic fluorescence quenching was observed in the case of glucose, while static quenching was observed in the case of methyl glyoxal and glyoxal. Similarly, employing deconvolution FT-IR spectroscopy and CD spectroscopy for determination of change in secondary structures in terms signature of α-helix, β-turn, β-sheet and random coil modifications. Destabilization or unfolding of the albumin structure, due to the disruption of the hydrogen bonding pattern that stabilizes the albumin manifold, causes a 25-50% reduction in α-helix and a 2-fold increase in β-sheet and turns in glycated BSA. The competitive displacement interaction studies with warfarin were performed using the ultrafiltration technique and quantitative determination of free drug in ultrafiltrate using LC-MS/MS. The binding of carbamazepine (CBZ) or its active metabolite to proteins was unaffected by the glycation of BSA with glucose and methyl glyoxal. Nevertheless, with glyoxal-modified BSA, it changed the binding of selected analytes significantly. Based on in vitro observations and results, it could be anticipated that the serum CBZ concentration variation may be worsened in uncontrolled diabetes circumstances, with an overall variance of 30–40% possible. Communicated by Ramaswamy H. Sarma

A comparative study of indocyanine green instillation in inguinal node versus foot web space using da Vinci indocyanine green FireFly™ technology in identifying thoracic duct during robotic-assisted transthoracic oesophagectomy.

Chyle leak is a serious complication following oesophagectomy with incidence varies from 1% to 9%. Near infra-red fluorescence imaging of thoracic duct (TD) can provide real-time dynamic imaging during the surgery. In this study, we intend to compare indocyanine green (ICG) dye instillation through inguinal node with subcutaneous first web space instillation for visualisation of TD during robotic-assisted minimally invasive oesophagectomy (RAMIE) procedure. A prospective study of 50 patients underwent RAMIE with da Vinci X System. After general anaesthesia, patients were divided into inguinal node and foot first web space ICG instillation group. The former group had 1 ml of ICG dye instilled on bilateral inguinal nodes under ultrasound guidance and while the other group received 1 mL of ICG dye injected at bilateral foot first web space and then underwent surgery. TD was visualised using ICG FireFly™ fluorescence technology, first at the time of docking and subsequently for every 5 min until 60 min of instillation time and analysed. Twenty-five patients were enrolled in each group. The mean docking time for thoracic phase was 13.76 ± 3.43 min. TD was visualised in 72% (18/25) of cases of first web space instillation group, whereas 100% in ultrasound guidance inguinal node instillation group. None of the patients had a chyle leak. ICG FireFly™ fluorescence technology for the identification of TD during oesophageal mobilisation is safe and effective and provides real-time dynamic visualisation with high accuracy in ultrasound-guided bilateral inguinal node instillation group. It is an effective method for the surgeons planning to negotiate their initial learning curve in RAMIE procedures.

Recent advances in Si-rhodamine-based fluorescent probes for live-cell imaging.

Fluorescence imaging is a powerful technique for visualizing biological events in living samples with high temporal and spatial resolution. Fluorescent probes emitting far-red to near infrared (NIR) fluorescence are particularly advantageous for in vivo imaging due to their high tissue permeability and low autofluorescence, as well as their suitability for multicolor imaging. Among the far-red to NIR fluorophores, Si-rhodamine is one of the most practical fluorophores for the development of tailor-made NIR fluorescent probes because of the relative ease of synthesis of various derivatives, the unique intramolecular spirocyclization behavior, and the relatively high water solubility and high photostability of the probes. This review summarizes these features of Si-rhodamines and presents recent advances in the synthesis and applications of far-red to NIR fluorescent probes based on Si-rhodamines, focusing on live-cell imaging applications such as fluorogenic probes, super-resolution imaging and dye-protein hybrid-based indicators.

Pectin-stabilized silver nanoparticles: synthesis, optical and antimicrobial activity against E. Coli

Nanoparticles synthesis using biomaterials is gaining popularity due to their biocompatibility, green approach and environmentally friendly nature. In this study, we report for the first time a simple and rapid synthesis of silver nanoparticles (AgNPs) via a one-step green approach using pectin obtained from the pulp of Parkia biglobosa as a novel reducing and stabilizing agent, which can serve as sustainable and economically viable alternative to conventional synthesis. The synthesized nanoparticles were characterized using Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), UV–Visible Spectrophotometer, Fourier Transform Infra-Red (FTIR) and Energy Dispersive X-ray Fluorescence (EDXRF) Spectroscopy. Different factors affecting AgNPs synthesis were studied by varying the volume of pectin solution, concentration of silver nitrate (AgNO3) and pH of the reaction. Optimum conditions for the synthesis of AgNPs were found to be at a pH of 12, 10 mM AgNO3 concentration and 3 mL pectin solution. Photoluminescence study showed that AgNPs formation began within 5 min of the reaction time under sunlight. Analysis of SEM and TEM suggested the formation of well dispersed silver nanoparticles with average particle size within 20–30 nm. The AgNPs showed antibacterial activities against Escherichia coli. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were found to be 50 and 100 µg/mL respectively. The study indicates that AgNPs synthesized using pectin from P. biglobosa exhibit great potential for applications in biomedicine, catalysis, bioremediation and food preservation.

NIR-II emissive nanoprobe for non-invasive monitoring of liver fibrosis and in-situ ratiometric visualization of NO gas-based therapy process

Timely detecting the progression and therapeutic effect of non-alcoholic liver disease is a great challenge due to lacking suitable non-invasive imaging methods. Herein, a novel theranostic nanoplatform based on lanthanide nanorods integrated with photo-triggered NO releasing molecule (NaYF4:Gd/Yb/Er@mSiO2-RBS) is designed for simultaneous diagnosis of liver fibrosis and second near infrared (NIR-II) ratiometric fluorescence imaging of the NO gas-based therapy of liver fibrosis. The mice with liver fibrosis present bright NIR-II emission (1000–1400 nm) via endogenous pigment secreted in liver fibrosis area under 808 nm laser excitation, enabling non-invasive diagnosis of liver fibrosis. In addition, the nanoplatform presents efficient NO gas release for therapy of liver fibrosis and 1532 nm emission activated by 980 nm laser. Importantly, after NO gas therapy, NIR-II fluorescent signal of the endogenous pigment was decreased, while the fluorescent signal around 1532 nm was increased, leading to the specific ratiometric NIR-II imaging of the therapy process with high specificity. Thus, the developed theranostic nanoprobe provided a powerful tool for timely NIR-II ratiometric detecting the progression and therapeutic effect of liver disease.

(Invited) Near Infrared Fluorescence Lifetime Imaging of Biomolecules with Carbon Nanotubes

Single wall carbon nanotubes (SWCNTs) are versatile building blocks for biosensors. Their near infrared (NIR) fluorescence enables detection of biomolecules in the optical tissue transparency window. Their surface chemistry can be tailored to selectively interact with analytes, which typically changes the fluorescence intensity. However, such signals are affected by external factors such as sample movement or fluctuations in excitation light. Here, we demonstrate fluorescence lifetime imaging microscopy (FLIM) of SWCNT-based sensors in the NIR as absolute and calibration-free method.For this purpose, we use a tailored laser scanning confocal microscope (LSCM) optimized for NIR signals (>800 nm) and time correlated single photon counting (TCSPC). (GT)10-DNA modified SWCNTs serve as sensor of the important neurotransmitter dopamine. The detected fluorescence signal > 900 nm increases in lifetime up to 25 %. These lifetime sensors are used as paint to cover cells and report extracellular dopamine in 3D. We therefore show the potential of using fluorescence lifetime in combination with confocal microscopy as readout for SWCNT-based sensors.

(Invited) Stochasticity in the Number of Quantum Defects in Fluorescent Carbon Nanotubes

Single wall carbon nanotubes (SWCNTs) display chirality dependent near infrared (NIR) fluorescence. Their optoelectronic properties can be further tuned by incorporating quantum defects/organic color centers (OCC) via reactions with diazonium salts. The absolute number of defects per SWCNT determines the properties but is not exactly known. Measuring it is complicated because typical SWCNT samples contain multiple chiralities, that congest the spectra and prevents to distinguish defects from different chiralities. Aqueous two-phase extraction (APTE) is a powerful technique to isolate specific chiralities. Here, we show that quantum defects do not affect APTE, which indicates that the chemical potential is not substantially affected and pinpoints to low numbers of defects. The purity of (6,5)-SWCNTs allows us to image the NIR fluorescence contributions (E11 below 1050 nm, and E11 * above 1050 nm) on the single SWCNT level and defect incorporation itself on the single molecule level. Interestingly, one observes a stochastic distribution of the numbers of defects, which can be explained by a Poisson distribution. We find a mean number of defects of 0-3 per SWCNT. These results indicate the large variance between ensemble and single particle picture. In summary, we show that single quantum defects can be counted by NIR imaging and that stochasticity plays a crucial role for their optical properties.

Ambient Light Resistant Shortwave Infrared Fluorescence Imaging for Preclinical Tumor Delineation via the pH Low-Insertion Peptide Conjugated to Indocyanine Green.

Shortwave infrared (900-1,700 nm) fluorescence imaging (SWIRFI) has shown significant advantages over visible (400-650 nm) and near-infrared (700-900 nm) fluorescence imaging (reduced autofluorescence, improved contrast, tissue resolution, and depth sensitivity). However, there is a major lag in the clinical translation of preclinical SWIRFI systems and targeted SWIRFI probes. Methods: We preclinically show that the pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG), currently in clinical trials, is an excellent candidate for cancer-targeted SWIRFI. Results: pHLIP ICG SWIRFI achieved picomolar sensitivity (0.4 nM) with binary and unambiguous tumor screening and resection up to 96 h after injection in an orthotopic breast cancer mouse model. SWIRFI tumor screening and resection had ambient light resistance (possible without gating or filtering) with outstanding signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values at exposures from 10 to 0.1 ms. These SNR and CNR values were also found for the extended emission of pHLIP ICG invivo (>1,100 nm, 300 ms). Conclusion: SWIRFI sensitivity and ambient light resistance enabled continued tracer clearance tracking with unparalleled SNR and CNR values at video rates for tumor delineation (achieving a tumor-to-muscle ratio above 20). In total, we provide a direct precedent for the democratic translation of an ambient light resistant SWIRFI and pHLIP ICG ecosystem, which can instantly improve tumor resection.

Crystallization Kinetics: Relationship between Crystal Morphology and the Cooling Rate—Applications for Different Geological Materials

Crystal morphology is controlled by several physicochemical parameters such as the temperature, pressure, cooling rate, nucleation, diffusion, volatile composition, and viscosity. The development of different crystal morphologies is observed as a function of the cooling rate in many different rock types (i.e., glassy volcanic rocks, and archeometallurgical slags). Crystallization is a two-stage kinetic process that begins with the formation of a nucleus and then continues with the accumulation of ions on it. The shapes of the crystals depend on the degree of undercooling (ΔT), and euhedral crystals, having characteristic forms that reflect their crystallographic internal structure, that grow just below their liquidus temperature. In this study, crystal morphologies in different minerals (e.g., quartz, sanidine, olivine, pyroxene, magnetite, etc.) that had developed in silicic volcanic rocks (spherulites) and slags from ancient mining were investigated and characterized using optical microscopy, X-ray diffraction, and Fourier-transform infrared (FTIR), Raman, and scanning electron microscope-energy dispersive X-ray fluorescence (SEM-EDX) spectroscopic techniques. Depending on the increase in the cooling rate, quartz, feldspar, olivine, pyroxene, and magnetite minerals were found to crystallize in subhedral, skeletal, dendritic, spherical, bow-tie and fibrous forms in glassy volcanic rocks and archeometallurgical slags.

Remote Sensing Monitoring of Rice Diseases and Pests from Different Data Sources: A Review

Rice is an important food crop in China, and diseases and pests are the main factors threatening its safety, ecology, and efficient production. The development of remote sensing technology provides an important means for non-destructive and rapid monitoring of diseases and pests that threaten rice crops. This paper aims to provide insights into current and future trends in remote sensing for rice crop monitoring. First, we expound the mechanism of remote sensing monitoring of rice diseases and pests and introduce the applications of different commonly data sources (hyperspectral data, multispectral data, thermal infrared data, fluorescence, and multi-source data fusion) in remote sensing monitoring of rice diseases and pests. Secondly, we summarize current methods for monitoring rice diseases and pests, including statistical discriminant type, machine learning, and deep learning algorithm. Finally, we provide a general framework to facilitate the monitoring of rice diseases or pests, which provides ideas and technical guidance for remote sensing monitoring of unknown diseases and pests, and we point out the challenges and future development directions of rice disease and pest remote sensing monitoring. This work provides new ideas and references for the subsequent monitoring of rice diseases and pests using remote sensing.

Multimodality PET and Near-Infrared Fluorescence Intraoperative Imaging of CEA-Positive Colorectal Cancer

PurposeMolecular imaging is a major diagnostic component for cancer management, enabling detection, staging of disease, targeting therapy, and monitoring the therapeutic response. The coordination of multimodality imaging techniques further enhances tumor localization. The development of a single agent for real-time non-invasive targeted positron emission tomography (PET) imaging and fluorescence guided surgery (FGS) will provide the next generation tool in the surgical management of cancer.ProceduresThe humanized anti-CEA M5A-IR800 “sidewinder” (M5A-IR800-SW) antibody-dye conjugate was designed with a NIR 800 nm dye incorporated into a PEGylated linker and conjugated with the metal chelate p-SCN-Bn-deferoxamine (DFO) for zirconium-89 PET imaging (89Zr, half-life 78.4 h). The dual-labeled 89Zr-DFO-M5A-SW-IR800 was evaluated for near infrared (NIR) fluorescence imaging, PET/MRI imaging, terminal tissue biodistribution, and blood clearance in a human colorectal cancer LS174T xenograft mouse model.ResultsThe 89Zr-DFO-M5A-SW-IR800 NIR fluorescence imaging showed high tumor targeting with normal liver uptake. Serial PET/MRI imaging was performed at 24 h, 48 h, and 72 h and showed tumor localization visible at 24 h that persisted throughout the experiment. However, the PET scans showed higher activity for the liver than the tumor, compared to the NIR fluorescence imaging. This difference is an important finding as it quantifies the expected difference due to the sensitivity and depth of penetration between the 2 modalities.ConclusionsThis study demonstrates the potential of a pegylated anti-CEA M5A-IR800-Sidewinder for NIR fluorescence/PET/MR multimodality imaging for intraoperative fluorescence guided surgery.

SWIR Fluorescence Imaging In Vivo Monitoring and Evaluating Implanted M2 Macrophages in Skeletal Muscle Regeneration

Skeletal muscle has a robust regeneration ability that is impaired by severe injury, disease, and aging, resulting in a decline in skeletal muscle function. Therefore, improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders. Owing to their significant role in tissue regeneration, implantation of M2 macrophages (M2Mø) has great potential for improving skeletal muscle regeneration. Here, we present a short-wave infrared (SWIR) fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2Mø transplantation. SWIR fluorescence imaging was employed to track implanted M2Mø in the injured skeletal muscle of mouse models. It is found that the implanted M2Mø accumulated at the injury site for two weeks. Then, SWIR fluorescence imaging of blood vessels showed that M2Mø implantation could improve the relative perfusion ratio on day 5 (1.09 ± 0.09 vs 0.85 ± 0.05; p = 0.01) and day 9 (1.38 ± 0.16 vs 0.95 ± 0.03; p = 0.01) post-injury, as well as augment the degree of skeletal muscle regeneration on day 13 post-injury. Finally, multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration. These results provide more in vivo details about M2Mø in skeletal muscle regeneration and confirm that M2Mø could promote angiogenesis and improve the degree of skeletal muscle repair, which will guide the research and development of M2Mø implantation to improve skeletal muscle regeneration.

Choledochal cyst.

Choledochal cyst (CC) or congenital biliary dilatation, has a skewed distribution with hereditary features that is far more common in East Asian females. CC is usually associated with pancreaticobiliary malunion (PBMU) forming a common channel. CC requires early definitive diagnosis, since there is a risk for malignancy occurring in the CC and/or intrahepatic bile ducts (IHBD). Complete CC excision and Roux-en-Y hepaticoenterostomy is required and can be performed by open or minimally invasive surgery with hepatojejunostomy the recommended procedure of choice. Principles of open surgical intervention form the basis of minimally invasive management with laparoscopy and robotic assistance. Current surgical management is associated with fewer early and late complications, such as hepaticoenterostomy anastomotic leakage, cholangitis, anastomosis stricture, and cholangiocarcinoma. Specific features of CC management at Juntendo include: intraoperative endoscopy of the common channel and IHBD for inspecting and clearing debris to significantly reduce post-operative pancreatitis or stone formation; near infra-red fluorescence with indocyanine green for visualizing tissue planes especially during minimally invasive surgery for CC; and a classification system for CC based on PBMU that overcomes inconsistencies between existing classification systems and clinical presentation.

Rapid Assessment of Fish Freshness for Multiple Supply-Chain Nodes Using Multi-Mode Spectroscopy and Fusion-Based Artificial Intelligence.

This study is directed towards developing a fast, non-destructive, and easy-to-use handheld multimode spectroscopic system for fish quality assessment. We apply data fusion of visible near infra-red (VIS-NIR) and short wave infra-red (SWIR) reflectance and fluorescence (FL) spectroscopy data features to classify fish from fresh to spoiled condition. Farmed Atlantic and wild coho and chinook salmon and sablefish fillets were measured. Three hundred measurement points on each of four fillets were taken every two days over 14 days for a total of 8400 measurements for each spectral mode. Multiple machine learning techniques including principal component analysis, self-organized maps, linear and quadratic discriminant analyses, k-nearest neighbors, random forest, support vector machine, and linear regression, as well as ensemble and majority voting methods, were used to explore spectroscopy data measured on fillets and to train classification models to predict freshness. Our results show that multi-mode spectroscopy achieves 95% accuracy, improving the accuracies of the FL, VIS-NIR and SWIR single-mode spectroscopies by 26, 10 and 9%, respectively. We conclude that multi-mode spectroscopy and data fusion analysis has the potential to accurately assess freshness and predict shelf life for fish fillets and recommend this study be expanded to a larger number of species in the future.

Acceptor/π-bridge planarization and donor rotation manipulation for designing an NIR-II AIEgen with high photothermal conversion efficiency to enhance cancer phototherapy

Aggregation-induced emission luminogens (AIEgens) with second near infrared (NIR-II) fluorescence and photothermal therapy (PTT) have recently attracted great research interest. The formidable challenge, the competing balance between radiation-mediated NIR-II fluorescence imaging and non-radiation NIR-PTT, prevents the development of efficient NIR-II AIEgens. In this study, a quite strong photothermal agent TPTQ is developed via rational design, which involves planarizing acceptor and π-bridge and rotating donor. The strong electron-withdrawing moiety 6, 7-diphenyl-[1,2,5]thiadiazolo[3,4-g]quinoxaline is selected as the acceptor and thiophene is fabricated as the π-bridge. The planarization of π-bridge and acceptor units can enhance the intramolecular charge transfer effect, which makes TPTQ possess a long imaging wavelength longer than 1300 nm. Moreover, phenothiazine is utilized as the donor and triphenylamine is engineered on the donor part as a rotor to optimize the AIE-active characteristic and photothermal conversion efficiency of TPTQ. Notably, the TPTQ nanoparticles (NPs) achieve the highest photothermal conversion efficiency of 73.32% among the reported photothermal agents with NIR-II fluorescence imaging capability. Extensive tests in vivo indicate that the constructed TPTQ NPs can not only serve as a superior NIR-II fluorescence imaging (FLI) for the blood vessels of mice but also be successfully applied in 4T1 tumor-xenografted mice for the outstanding photothermal imaging (PTI), demonstrating distinguished FLI-guided photothermal tumoricidal capability. Herein, the smart design of acceptor/π-bridge planarization and donor rotation provide a new approach of developing highly effective NIR-II photothermal therapeutic agents.

Viscosity-triggered near-infrared fluorescence nanoprobe for in vivo non-invasive diagnosis of cancer

A universal and non-invasive approach for cancer diagnosis is desired to lessen the burden of cancer mortality. In this work, we exploited viscosity in the cancer microenvironment as a diagnosis indicator and designed a universal probe, the CBT-Q (4-(2-(5-(9-(4-aminophenyl)-9H-carbazol-3-yl) thiophen-2-yl)vinyl)-1-ethylquinolin-1-ium) nanoprobe, for detecting viscosity variation in the cells, plasma, and solid tumor-mice to obtain a cancer diagnosis. The near infrared (NIR) fluorescence of CBT-Q was specifically triggered due to a change in its structure from a flexible to a rigid one in the presence of a higher viscosity agent, such as a cancer microenvironment or cancer patient plasma. The Stokes shift of CBT-Q nanoprobe (CBT-Q-N) could be up to 178 nm, enabling the diagnosis of cancer with a low biological fluorescent background. Not only could the CBT-Q-N remain in cells for 72 h, but detect the changes in cell viscosity induced by various models. Also, the CBT-Q-N differentiated early and terminal tumor mice via the fluorescent intensity of plasma viscosity. The CBT-Q-N enables non-invasive recognition of tumors in vivo by fluorescence imaging. Hence, this work is beneficial to increase the understanding of tumor-related viscosity, which will facilitate a new universal strategy for present cancer diagnostics.