Croconium Dye Research Articles

Acidic Lysosome-Anchoring Croconium-Based Nanoplatform for Enhanced Triple-Mode Bioimaging and Fe3+-Triggered Tumor Synergistic Therapy.

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe3+-modulated agent. The established CR-736-Fe3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H2O2 by dint of the accumulation of Fe3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.

Comparison of a series of donor-acceptor-donor type croconium dyes on pH response, near-infrared fluorescence/photoacoustic imaging and photothermal properties

Eight donor-acceptor-donor type croconium dyes with different donor moieties, such as indole, N-methylindole, benzo[e]indole, N-methylbenzo[c,d]indole, benzothiazole and quinoline groups, have been designed and discussed their pH response, near-infrared fluorescence/photoacoustic (NIR/PA) imaging and photothermal properties in solutions and tumor cells. Croconium dye with bisbenzothiazole CBT exhibited the best NIR-imaging. Croconium dye with bisindole CBI-1 showed the best PA-imaging. Dye CBI-3 with bisbenzo[e]indole showed the best photothermal. Four dyes with either indole or benzo[e]indole group CBI-1, CBI-3, CIT and CIQ showed pH response on fluorescence and photoacoustic spectra and photothermal. This study proves that preserving the indole group in croconium dyes was beneficial for their pH response and NIR/PA imaging, and the introduction of quinoline and thiazole groups was detrimental to the photostability. Gathered with pH response, NIR/PA imaging and photothermal property, dye CBI-1 is suitable for structural modification in the future for developing better cancer theranostic reagents.

Programmably Controllable Delivery of Metastable Ferrous Ions for Multiscale Dynamic Imaging Guided Photothermal Primed Chemodynamic Therapy.

Metallomodulation cell death strategies are extensively investigated for antitumor therapy, such as cuproptosis, ferroptosis, and chemodynamic therapy (CDT). Undoubtedly, the accurate and specific elevation of metal ions levels in cancer cells is key to boosting theirtherapeutic index. Herein, a programmably controllable delivery system based on croconium dye (Croc)-ferrous ion (Fe2+ ) nanoprobes (CFNPs) is developed for multiscale dynamic imaging guided photothermal primed CDT. The Croc, with kinds of electron-rich iron-chelating groups, can form the Croc-Fe2+ complex with a precise stoichiometry of 1:1 to steadily maintain the valence state of Fe2+ . The CFNPs can achieve pH-responsive visualization and accurate Fe2+ release in cancerous tissues under the coactivation of "dual-key" stimulation of "acidity and near-infrared (NIR) light". The acidic tumor microenvironment actuates NIR fluorescence/photoacoustic imaging and photothermal properties of CFNPs. Sequentially, under exogenous NIR light, the CFNPs enable in vivo accurate visualization of Croc-Fe2+ complex delivery for photothermal primed Fe2+ release, thus achieving CDT of tumors. By leveraging multiscale dynamic imaging technologies, the complicated spatiotemporal release of Fe2+ is sketched in a programmably controllable manner, and the domino effect of tumor pH level, photothermal effect, and CDT is also revealed, endowing customized feedback of the therapeutic panorama within the disease microenvironment.

A highly sensitive and selective colorimetric/fluorescent probe for the detection of Ag+ based on a croconium dye

A novel colorimetric and fluorescent probe, 2,5-bis[3-ethyl-2-methylbenzothiazole]-croconine (BBC) has been synthesized and characterized. The BBC dye can effectively recognize Ag+ in the presence of potentially competitive metal ions (Co2+, Na+, Cd2+, K+, Mg2+, Zn2+, Ca2+, Ba2+, Ni2+, Cr3+, Al3+), which exhibited visible color change and fluorescence spectra behaviors. The Benesi-Hildebrand plot accurately showed the binding constant of BBC-Ag+. Correspondingly, the 1:1 stoichiometric structure of BBC and Ag+ was evaluated by using Job’s plot. Moreover, the complex mechanism of BBC toward Ag+ were also investigated by Fourier transform infrared (FT-IR) and 1H nuclear magnetic resonance (1H NMR). The results indicated that BBC could be used as a high effective colorimetric and fluorescent sensor to identify Ag+.

Highly photostable croconium dye-anchored cell membrane vesicle for tumor pH-responsive duplex imaging-guided photothermal therapy

The development of tumor acidic microenvironment-responsive theranostic agents is a research hotspot. Herein, we developed highly photostable amphiphilic croconium dye-anchored red blood cell membrane vesicle (denoted as LET-5) for tumor pH-responsive near-infrared fluorescence (NIRF) and photoacoustic (PA) duplex imaging-guided photothermal therapy. In tumor acidic microenvironment, both NIRF and PA signals of LET-5 were significantly enhanced and the photothermal effect of LET-5 was activated. Notably, cell membrane-based vesicle with enhanced stability and long blood circulation significantly improved the tumor accumulation of croconium dye, thus achieving better therapeutic effect than free croconium dye. These findings provide a promising approach to construct amphiphilic dye-anchored cell membrane vesicle for cancer theranostics.

Highly specific noninvasive photoacoustic and positron emission tomography of brain plaque with functionalized croconium dye labeled by a radiotracer.

Highly-efficient targeting probes are desirable for disease diagnosis and functional imaging. However, most of the current near-infrared (NIR) probes suffer from low signal conversion, insufficient photostability, poor probe specificity, and limited functions. Herein, an NIR ultrahigh absorbing croconium dye for amyloid (CDA) was designed and synthesized to specifically bind to cerebrovascular amyloid without antibody linkage. This unique CDA is able to strongly bind the hydrophobic channels of amyloid beta (Aβ) fiber with a very strong binding energy of -9.3 kcal mol-1. Our experimental results demonstrate that the amphipathic dye with an intense absorption peak at 800 nm generated a significant local temperature surge under low-power laser irradiation. Compared with representative prominent indocyanine green, Prussian blue, and gold nanorods, this probe can produce the strongest photoacoustic signal based on the same mass concentration. Labeled with radioactive 18F, this multifunctional probe allowed for the ultrasensitive photoacoustic tomography (PAT)/positron emission tomography (PET)/fluorescence imaging of Aβ plaques in the brain cortex. Featured with high spatial resolution and optical specificity, PAT was intrinsically suitable for imaging pathological sites on cortical vessels, whereas PET revealed whole-body anatomy with quantitative biodistribution information. Our study shows that a CDA-based functionalized dye aided with PAT and PET is capable of plaque diagnosis and localization.

Dual colorimetric and fluorescent chemosensor of Fe3+ and Cu2+ based on 2,5-bis[(4-carboxylic-piperidylamino)thiophenyl]-croconine

A croconium dye, 2,5-bis[(4-carboxylic-piperidylamino)thiophenyl]-croconine (BCTC) based dual signaling probe was found to exhibit colorimetric and fluorescent properties on selective binding towards Fe3+ and Cu2+ in ethanol/water (4:1, v/v) solution, respectively. The binding constants were determined to be 2.12×104 M−1 and 8.58×104 M−1 for Fe3+ and Cu2+, respectively. Most importantly, the 1:1 stoichiometry of the host-guest complexation was confirmed by Job's method. This result was further confirmed by 1H NMR analysis. Meanwhile, the selectivity experiments revealed that the colorimetric and fluorescent sensor were specific for Fe3+ and Cu2+ even with interference by high concentrations of other metal ions. Moreover, the sensing abilities of the receptor toward Fe3+ and Cu2+ were also investigated by electrochemical technique. The present results indicated that the BCTC chemosensor could be adopted as a selective, sensitive and reversible colorimetric and fluorescent sensor for Fe3+ and Cu2+.

Progress in the Studies of Croconium Dyes

Croconium dye is an important part in the cyanine family used as organic function dye, which has been attracted extensive attention recently because of its strong and sharp absorption, large molar absorption coefficient and good photo- chemical stability in the near-infrared region. The unique structure, and physical and chemical properties, together with the recent progress in the preparation methods of croconium dyes are reviewed. The promising application in the fields of optical materials, biology, medicine, etc. is also introduced. Keywords croconium dye; structure; property; synthesis; application

Croconium dye as a sensitizer of photothermoplastic holographic media for the near-IR region

This paper discusses the spectral and photoconductive properties of films based on a co-oligomer of glycidylcarbazole with additives of croconium dye in comparison with similar films with squarylium, merocyanine, and cationic polymethine dyes. It is concluded that croconium dye, like merocyanine dye, belongs to the electron-nonsymmetric organic dyes. The possibility of using croconines as sensitizers of photothermoplastic holographic recording media for the near-IR region is demonstrated for the first time. The lower holographic sensitivity of recording media with croconium dye by comparison with squarylium and merocyanine dyes is associated with the presence of deep traps for charge carriers, which are formed by the molecules of an intraionic dye and are liberated when heated in the process of development of the holograms.

A new water-soluble near-infrared croconium dye

A new water-soluble near-infrared (NIR) absorbing croconium dye, 2,5-bis[(4-carboxylic-piperidylamino)thiophenyl]-croconium, was synthesised by condensing croconic acid with 2-(4-carboxylic-piperidylamino)thiophene and characterised by 1H NMR, high-resolution MS and UV–vis spectra. The dye showed a sharp and intense absorption band peaking near 800 nm and little absorption in visible region in several water-soluble polymers. It also exhibited excellent photostability in water, methanol and in the plastic films. Due to its good water solubility, a water-based coating process was developed to make NIR blocking plastic filters for use as attenuators of stray light in NIR laser systems.

A near-infrared croconium dye-based colorimetric chemodosimeter for biological thiols and cyanide anion

A near-infrared colorimetric chemodosimeter based on a croconium dye, 1,3-bis(4-N,N-diethylamino-2-hydroxyl-phenyl) croconine, was developed to selectively and sensitively probe cysteine, homocysteine, or cysteine–glycine at pH 5.7 and cyanide anion at pH 9.0 in aqueous ethanol solutions.

Resonant third-order optical nonlinearities of 1,3-bis[(3,3-dimethylindolin-2-ylidene)methyl]croconine

The third-order optical nonlinearities and responses of a croconium dye (1,3-bis[(3,3-dimethylindolin-2-ylidene)methyl]croconine) in tetrahydrofuran (THF) solution and in poly(methyl methacrylate) (PMMA) coating films were measured using a femtosecond degenerate four-wave mixing (DFWM) technique with a time resolution of 0.3 ps (FWHM) system under resonant conditions. The electronic component of molecular hyperpolarizability, γ e of the croconium dye in THF solution was determined to be about 5.3×10 −29 esu at 773 nm. The electronic component of third-order nonlinear optical susceptibilities, χ e ( 3 ) of the present PMMA coating films containing the croconium dye was measured to be of the order of 10 −8 esu, and the figure of merit of third-order nonlinearity F ( F = χ ( 3 ) / α ) , was evaluated to be about 8.3×10 −14 esu cm. The χ e ( 3 ) for a neat film was about 4.9×10 −8 esu at 820 nm.

Large Third-Order Optical Nonlinearities of a Croconium Dye in Tetrahydrofuran Solution and in Poly(methyl methacrylate) Coating Films Measured Using Resonant Femtosecond Degenerate Four-Wave Mixing Technique

The third-order optical nonlinearities of a croconium dye in tetrahydrofuran (THF) solution and in poly(methyl methacrylate) (PMMA) coating films were measured using the femtosecond degenerate four-wave mixing (DFWM) technique under resonant conditions. The temporal profiles of the DFWM signal of the croconium dye were obtained with a time resolution of 0.3 ps (FWHM), and were found to consist of at least two components, i.e., the coherent instantaneous nonlinear response (electronic response) and the slow response due to the formation of excited molecules for both the THF solution and PMMA coating films. The electronic component of molecular hyperpolarizability, γe, of the croconium dye in the THF solution was determined to be ca. 4.6×10-29 esu at 817 nm. The electronic component of third-order nonlinear optical susceptibility, χ(3)e, of one of the present PMMA coating films containing the croconium dye was ca. 1.3×10-8 esu at 824 nm.